Press Releases: 2007

Cancer Research Giants Collaborate to Present The CTRC-AACR San Antonio Breast Cancer Symposium

registration@aacr.org () — Thu, 13 Dec 2007 12:00:00 GMT

Partnership creates the largest and most comprehensive symposium of its kind by blending basic, translational and clinical research related to breast cancer

SAN ANTONIO - The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio and the American Association for Cancer Research (AACR) announced today a collaboration for the future of the San Antonio Breast Cancer Symposium (SABCS). The announcement came at the 30th Annual Charles A. Coltman Jr. San Antonio Breast Cancer Symposium, held at the Henry B. Gonzalez Convention Center in San Antonio. As a result of the collaboration, the symposium will be renamed the CTRC-AACR San Antonio Breast Cancer Symposium beginning in 2008. Complementing the clinical strengths of the highly regarded annual San Antonio Breast Cancer Symposium, the AACR's scientific prestige in basic, translational and clinical cancer research will create a unique and comprehensive scientific meeting that will advance breast cancer research for the benefit of patients.

The San Antonio Breast Cancer Symposium attracts academic and private physicians and researchers, as well as other health care professionals focused on curing breast cancer, to discuss and learn about new and late-breaking research including experimental biology, etiology, prevention, diagnosis, and therapy of breast cancer and pre-malignant breast disease, as well as new findings from clinical trials. A primary goal of the CTRC-AACR collaboration is to attract to the meeting more thought-leaders and high-quality proffered papers in basic and translational breast cancer research. Another key goal is to increase the participation of young investigators by providing superior education and training opportunities for the next generation of breast cancer researchers.

The driving force behind the collaboration is the shared mission of the partners to advance progress against breast cancer. By combining their respective strengths, the partnership will produce a scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for breast cancer patients.

"As the founder of the SABCS, the CTRC and The University of Texas Health Science Center at San Antonio will work together with the AACR to provide a unique forum for the scholarly discussion of the latest advances in the etiology, prevention and treatment of breast cancer," said Karen K. Fields, M.D., president and chief executive officer at CTRC. "SABCS is arguably the best breast cancer research meeting in the world, and with the addition of AACR's high-quality science, credibility and outreach, this collaboration will be synergistic and garner further scientific prominence."

"The AACR is delighted to have the opportunity to partner with CTRC and Baylor College of Medicine in presenting this meeting to the breast cancer community," said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer at AACR. "The San Antonio Breast Cancer Symposium is already an outstanding meeting. Clearly, the expert input of the AACR will enhance interactions between basic and clinical researchers and expedite the delivery of the latest scientific advances into the clinic."

Under the terms of a mutual agreement between The University of Texas Health Science Center at San Antonio and AACR, the AACR will contribute to program development and oversight of the CTRC-AACR San Antonio Breast Cancer Symposium. The AACR will also create and obtain funding for a new award and lecture for outstanding breast cancer research conducted by a young investigator. In addition, the AACR will support scholar-in-training awards for meeting attendance by early-career and minority scientists.

In 2005, Baylor College of Medicine (BCM) became a joint sponsor of the symposium and will remain in the CTRC-AACR collaboration. C. Kent Osborne, M.D., director of the Dan. L. Duncan Cancer Center at BCM, will continue to serve as SABCS chair and three co-chairs will represent each of the partners. The program planning committee of the CTRC-AACR San Antonio Breast Cancer Symposium will have broad representation by national and international breast cancer experts.

The 2007 San Antonio Breast Cancer Symposium is expected to draw nearly 8,300 participants from more than 80 countries and runs from December 13 to 16, 2007.

###

About the Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio
Located in San Antonio, Texas, the Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the nation's leading academic research and treatment centers, serving more than 4.4 million people in the high-growth corridor of Central and South Texas including Austin, San Antonio, Laredo, and the Rio Grande Valley. CTRC is one of a few elite cancer centers in the country to be named a National Cancer Institute (NCI) Designated Cancer Center, and is one of three in Texas. CTRC handles more than 120,000 patient visits each year and is a world leader in developing new drugs to treat cancer. The CTRC Institute for Drug Development (IDD) is internationally recognized for conducting the largest oncology Phase I clinical drug trials program in the world, and participated in the clinical and/or preclinical development of many of the cancer drugs approved by the Food & Drug Administration. For more information visit our website at www.ctrc.net.

About the American Association for Cancer Research
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes over 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the etiology, prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

About Baylor College of Medicine
Baylor College of Medicine in Houston, the only private medical school in the Greater Southwest, was founded in 1900 and is today an internationally respected medical and research institution known for excellence in education, research and patient care. Located in the Texas Medical Center, a 1,000-acre complex housing 46 member institutions, BCM has affiliations with eight teaching hospitals, each with a national and international reputation for medical excellence. The college has total research support of $374 million, with $314 million from federal sources, and more than 90 research and patient-care centers and units. Currently, BCM trains more than 3,000 medical, graduate, nurse anesthesia, and physician assistant students, as well as residents and post-doctoral fellows.

Contact:
Jill Byrd, CTRC (210) 450-5550
Staci Goldberg, AACR (267) 646-0616

Lifestyle and Cancer Prevention: Making Choices that Change Cancer Risk

registration@aacr.org () — Fri, 07 Dec 2007 12:00:00 GMT

PHILADELPHIA - How do the lifestyle choices we make affect our chances of developing cancer? Today, at the American Association for Cancer Research's Sixth Annual International Conference on Frontiers in Cancer Prevention Research, being held from December 5 to 8 in Philadelphia, Pennsylvania, researchers will present some answers to questions regarding daily decisions in diet, exercise, smoking and other lifestyle factors.

According to their findings, while genetics and environment are major contributors to cancer risk, the simple decisions made each day often matter too. Whether you are picking up a pack of cigarettes, a bottle of suntan lotion, or your walking pace, studies show the power to influence cancer risk is in your hands.

Diet and physical activity in lung cancer risk prediction for current, former, and never smokers. Abstract no. B143

People who have quit smoking can further reduce their risk of developing lung cancer by adding lots of vegetables to their diet - as measured by eating four or more servings of salads a week - compared to people who quit but do not eat their veggies, report researchers at The University of Texas M. D. Anderson Cancer Center. The investigators also found that physical activity like gardening reduces risk of developing the cancer in "former-smokers" by up to 45 percent, compared to former smokers who don't garden.

"We are trying to understand what components of lifestyle can reduce lung cancer risk in people who have quit smoking - which has been a neglected field of study," said Michele Forman, Ph.D., a professor of epidemiology at the University of Texas. "Although this is a very preliminary analysis, it gives us some important clues about how everyone - smokers and non-smokers alike - might be able to reduce their risk of developing lung cancer."

The research team also found that current smokers have a two-fold higher risk of developing lung cancer if they eat three servings or less of salad a week, compared to current smokers who do eat four or more salads weekly. Reduction of risk through gardening was about the same (33 percent) as seen in former smokers, they found. The investigators are also exploring the role of diet and physical activity in lung cancer risk for never-smokers.

"If you are worried about lung cancer risk, this study shows that you may benefit from eating a healthy diet and being physically active," Forman said.

The data come from M. D. Anderson's case control study of lung cancer, involving more than 3,800 participants. Its unique design matches lung cancer patients at M. D. Anderson with participants who are treated at a Houston HMO and divides them by smoking status. So, for example, a person who has never smoked but who developed lung cancer would be matched with a never-smoker who is cancer-free, and the same pairing process is done for former and current smokers with and without lung cancer. All participants are non-Hispanic whites.

The model has already identified a variety of epidemiologic risk factors for lung cancer due to exposure to second-hand smoke and to dust, family history of cancer, history of respiratory disease in the patient and smoking history. With those variables, the discriminatory power of the model was modest.

This study added diet and physical activity to the list of potential factors, making it the first risk prediction model to address both of these variables at the same time, Forman says. To do that, investigators asked participants about eating salad "because salad is a marker for consumption of many vegetables," and polled participants about gardening activity "because we found that gardening is one of the few activities that people with lung cancer report doing," she said.

According to Forman, the researchers do not know yet whether those habits of eating well and exercising "are a marker for other lifestyle factors that might be even more important, such as lack of alcohol consumption. We have a lot of puzzles in the picture yet to analyze."

Gender differences in antioxidant activity, DNA damage, and vasculature in ultraviolet light exposed skin. Abstract no. B144

A novel study in mice suggests that men are more prone to developing cancer than women because of gender differences in antioxidant levels and the ability to repair DNA damage.

Researchers at Ohio State University found that when exposed to the same degree of damaging ultraviolet (UV) light, the skin of male mice suffered more genetic damage than that of female mice. As a consequence, the male mice developed more squamous cell skin cancers, and these tumors formed faster and grew more aggressively than those that developed in the skin of female mice.

These results may explain why men develop three times as many squamous cell skin cancers as women do, and may also offer a clue as to why men are more prone to cancer development in general, says Kathleen Tober, Ph.D., a research scientist in Ohio State's Department of Pathology.

"Men get more skin cancer than women and it has classically been thought that the reason for this is lifestyle - men spend more time outside and are less likely to use sun protection," Tober said. "Our data suggests that while that may be a factor, an even more critical reason for this difference is that female skin may be better able to combat the damaging effects of UV exposure.

"Based on our data, it would be a reasonable hypothesis that one of the underlying mechanisms for this is that men might have less overall antioxidant levels and diminished DNA repair capacity," she said.

Approximately half of the 2 million-plus cancer cases diagnosed in the U.S. are non-melanoma skin cancers. Squamous cell carcinoma, with 250,000 new cases annually, is the second most common cancer in the country. While it is not always a fatal cancer, it does account for about 2,000 cancer deaths a year.

For years, the project's lead researcher Tatiana Oberyszyn, Ph.D., assistant professor at Ohio State's Department of Pathology has studied gender differences in non-melanoma skin cancer. She and her laboratory had initially discovered through controlled experiments that gender and its associated variables accounted for the difference between male and female rates of developing squamous cell carcinomas.

In this study, the researchers discovered that, to their surprise, male mice had less inflammation following exposure to UV light than did female mice, but they had increased oxidative DNA damage possibly due to insufficient levels of proteins that repair DNA damage.

"When equally exposed to sunlight, female skin turns pink and swells up - two classic signs of a sunburn," Tober said. "Male skin doesn't have as robust of a sunburn response to UV exposure but the genetic damage that male skin incurs is actually greater than female mice.

"Our data tells us that female skin has more antioxidants, compounds that scavenge DNA damaging chemicals, and potentially more mechanisms to repair DNA damage than male skin," she said. "These gender differences suggest that female skin has a higher capacity for repairing sunlight induced DNA damage than does male skin. Without complete repair of this genetic damage, male skin is more prone to skin cancer than is female skin."

These findings suggest that gender may need to be considered when it comes to controlling cancer, the researchers say. "Until those strategies are determined and whether you are male or female, it is best to take caution when it comes to sunlight exposure," Tober said.

Nicotine metabolism among African American and white smokers: Group and intraindividual differences in glucuronidation. Abstract no. B122

It has long been known that African-American smokers have a harder time giving up cigarettes, and now researchers from the University of Minnesota may have found a potential biochemical explanation.

Investigators discovered that African-American smokers may have significantly lower levels of an enzyme that metabolizes nicotine and nicotine by-products, compared to Caucasians who were exposed to identical nicotine patches. The findings suggest that African Americans may experience higher nicotine levels per cigarette, which would help explain why "quit" rates are lower among this group.

"Smokers adjust their level of smoking to maintain blood levels of nicotine, which are determined in part by rates of nicotine metabolism, and while we can't say from this study that differences in metabolism definitively account for lower quit rates, it could very well have an impact," said Jeannette Zinggeler Berg, an M.D./Ph.D. student in Biochemistry, Molecular Biology, and Biophysics at the University of Minnesota.

In past studies, elevated levels of the nicotine-related molecule, cotinine, have been observed in African-American smokers compared to Caucasian smokers. Cotinine is a direct metabolite of nicotine - a product of nicotine metabolism - and so it is a marker for exposure to tobacco, Berg says. "It is not carcinogenic and is not an addictive component of tobacco, but the more of it a person has in their blood, the more nicotine they have been exposed to," Berg said.

But researchers have debated whether differences in cotinine seen in African Americans is due to the common use of menthol cigarettes by the group, or to the fact that these smokers may be getting more nicotine per cigarette because they are smoking longer or inhaling more deeply.

In this study, Berg and her colleagues examined different markers of nicotine metabolism in 95 daily smokers who, during the study period, were required not to smoke and to wear a nicotine patch. They specifically looked at levels of glucuronides, which represent a pathway by which the liver metabolizes nicotine and cotinine, preparing these chemicals for urinary excretion. A low blood level of glucuronide can indicate an inefficient excretion pathway for nicotine, cotinine, and other substances such as pharmaceutical drugs, Berg says.

At the beginning of the study and after the participants started using the patch, nicotine metabolites were measured in urine samples. Both when subjects were smoking (baseline urine sample at the start of the study) or when they were on the nicotine patch, the percentage of cotinine in the glucuronide form was significantly lower among African Americans compared to Caucasian participants (at the start of the study: 66 percent versus 82 percent; on patch: 41 percent versus 62 percent). Glucuronidation of nicotine was also lower among African Americans compared to white participants on the patch (16 percent versus 30 percent).

"The higher levels of free cotinine seen in past studies between race groups could be explained by lower levels of glucuronide, which helps break down cotinine," Berg said. "If cotinine is a marker of nicotine in the blood, people with higher levels are more likely to have trouble giving up cigarettes."

Researchers are continuing the study by examining racial variation in two glucuronide enzymes in liver samples. "The differences we have seen could be explained by a number of factors, including environmental causes, and we hope to tease these influences apart," Berg said.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
267-646-0554
greg.lester@aacr.org
In the press room (December 5-8):
215-409-4766

Obesity and Metabolism: Weight Gain and the Growing Risk of Cancer

registration@aacr.org () — Fri, 07 Dec 2007 12:00:00 GMT

PHILADELPHIA - During this holiday season with its tempting bounty of edible delights, new research calls attention to the role of the expanding American waistline in health and medicine.

Today, researchers at the American Association for Cancer Research's Sixth Annual International Conference on Frontiers in Cancer Prevention Research, being held from December 5 to 8 in Philadelphia, Pennsylvania, present some of the latest research linking obesity, diabetes and metabolism to cancer risk. Their findings link weight gain and diabetes to a variety of cancers affecting both men and women, including breast, prostate and colorectal cancer.

Diabetes and hyper-insulinemia as predictors of colorectal cancer risk in a prospective cohort of women. Abstract no. B93:

Women with diabetes are 1.5 times more likely to develop colorectal cancer than those who do not have the metabolic disorder, according to researchers at the University of Minnesota. The findings, they say, add to the complex body of evidence linking diet and colorectal cancer and also provide new evidence that furthers our understanding of the role of insulin in cancer promotion.

"Colorectal cancer and type II diabetes share a number of common factors, including obesity, so it is interesting to see the direct line between these two conditions," said Andrew Flood, Ph.D., assistant professor in the Division of Epidemiology and Community Health at the University of Minnesota School of Public Health and the University of Minnesota Cancer Center "In general, the idea is that if elevated insulin levels create a biochemical environment conducive to cancer growth, it provides one mechanism by which diet and lifestyle can really influence cancer risk."

With funding from the National Cancer Institute, Flood and his colleagues examined data from a massive screening study called the Breast Cancer Detection Demonstration Project, initiated at 29 centers throughout the United States in the 1970s. Flood's team subsequently followed more than 45,000 study participants with no history of colorectal cancer or self-reported diabetes for eight years, (from 1987-1989 and from 1995-1998), to identify which of them subsequently developed colorectal cancer. According to their findings, women with diabetes had a greatly increased risk of developing colorectal cancer. "These results remained statistically significant even after controlling for all known and suspected confounding variables," Flood said.

According to Flood, it is not exactly clear what aspect of diabetes is the underlying cause for this increased risk, but one hypothesis centers on the elevated concentration of insulin typically seen in people with type II diabetes. "In the early stages of the disease process, people become insulin resistant, meaning they must produce more and more insulin to regulate their blood sugar," Flood said.

"Even after frank diabetes begins, insulin levels remain chronically elevated for extended periods before the pancreas can no longer supply the level of insulin the body demands," Flood said. "If the elevated insulin is the problem, then pre-diabetics, who are also hyper-insulinemic, should also be at increased risk (for developing colorectal cancer)."

To test that idea, Flood and his colleagues re-analyzed the data, this time including women who were likely pre-diabetic at the beginning of the follow-up period. The idea, Flood says, is that these women were likely hyper-insulinemic at that stage. Surprisingly, the elevated risk, while still significant, had dropped slightly in comparison with that of known diabetics, Flood says.

According to Flood, this suggests that either the pre-diabetic women had not had elevated insulin long enough or intensely enough to increase risk as they observed in the diabetic women, or alternatively, something other than or in addition to hyper-insulinemia could explain the significant, increased risk for colorectal cancer they observed in people with diabetes.

Fasting C-peptide levels and breast cancer death in women with breast cancer: The Health, Eating, Activity and Lifestyle (HEAL) Study. Abstract no. B99:

Women with invasive breast cancer and high blood levels of C-peptide (a marker of insulin secretion) face a risk of death nearly three times higher than women with lower blood levels of C-peptide, according to findings from the Health, Eating, Activity and Lifestyle (HEAL) Study, a long-term observational study of breast cancer patients. The effect was most notable, researchers say, among women in their 40s.

While previous research has demonstrated that insulin stimulates the growth of breast cancer cells in the laboratory, few studies have examined the link between fasting insulin or C-peptide levels and breast cancer prognosis. Women with invasive breast cancer - meaning the cancer had spread throughout the breast tissue or to surrounding tissues - faced the greatest risk from high C-peptide levels, the researchers say, but the association was detected in nearly all women studied, regardless of whether or not their cancer had spread.

"When looking at risk of diabetes and hypertension, breast cancer survivors really should talk to their oncologist about how to lower their insulin levels," said Melinda L. Irwin, Ph.D., M.P.H., assistant professor at Yale University's School of Public Health. "The simple message is that breast cancer patients should take proven steps to lower their blood insulin levels, including exercise and eating a diet rich in fruits and vegetables and low in fat."

The HEAL Study is a National Cancer Institute initiative designed to examine the links between diet, physical activity, body fat, and breast cancer prognosis. Patients enrolled in the HEAL Study -- including those participating in the study reported here - were diagnosed or treated at the Fred Hutchinson Cancer Research Center, the University of New Mexico or the University of Southern California.

Between 1995 and 1998, the researchers followed 689 women enrolled in the HEAL program who were diagnosed with breast cancer, but who did not have type 2 diabetes. They monitored their health at periodic intervals beginning six months after diagnosis until September 2004 or the patient's death. From each patient, they collected a fasting blood sample - a common technique for measuring a baseline of insulin or C-peptide levels - and information on prognostic, demographic, and lifestyle factors, including weight and height.

In order to determine the relationship between C-peptide levels and prognosis, Irwin and her colleagues statistically adjusted the data they collected for confounding variables such as body mass index, age, race, disease stage and therapy used in treatment. They found that, when arranged into three groups based on C-peptide levels, women in the top third of the group (highest levels) had twice the risk of death compared to women in the bottom third. When looking at just women with invasive breast cancer, the risk of death among women with high C-peptide levels was three times higher than among women with low C-peptide levels. "Our findings clearly show that C-peptide and most likely insulin, in and of itself, is a marker for breast cancer prognosis," Irwin said.

According to Irwin, the association was also common in women in their 40s with early stage breast cancer, and less pronounced in women in their 50s or 60s. "The higher death rate among younger women suggests that these women may have had more aggressive tumors, possibly related to tumor genetics or family history," said Irwin.

Association of C-peptide concentration with prostate cancer incidence in a prospective cohort. Abstract no. B89:

While studies have consistently shown that men with diabetes are at a decreased risk for prostate cancer, the reasons have been unclear. By evaluating prostate cancer data from a large, long-term cohort study, researchers at Johns Hopkins University have shown that those with high concentrations of C-peptide - a marker of high insulin secretion that is a hallmark of diabetes - had a measurable decrease in prostate cancer risk.

"Metabolic perturbations influence cancer risk, that much is becoming clear to us, and we are learning more about the fundamental issues in biology that guide prostate cancer development," said Gabriel Lai, a doctoral student in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. "One interesting possibility is that, over time, diabetics generally have less testosterone in their bloodstream than non-diabetics, which might lower risk of prostate cancer."

Lai and his colleagues used data from a large-scale study known as CLUE II, which had enrolled almost 23,000 adults in Washington County, Maryland in 1989. With funding from the National Cancer Institute, they examined the history of 264 men with confirmed prostate cancer and matched them with a group of 264 men without prostate cancer with a similar distribution of age and race.

For each participant, the researchers measured the amount of C-peptide in the blood they donated when they enrolled in the study. Researchers consider C-peptide to be a surrogate marker for insulin secretion because both molecules derive from the same precursor molecule, with insulin degrading faster than C-peptide. They found that patients that had elevated levels of C-peptide in their bloodstream when they started the study were about one-third less likely to develop prostate cancer later. This was true even among men without diabetes.

The researchers also report a markedly lower risk of non-metastasized prostate cancer. Men with higher C-peptide levels in their blood were half as likely to develop organ-confined prostate cancer, Lai says.

"Even though diabetes and obesity are often linked to different types of cancer, our findings illustrate the idea that the link between cancer and metabolic diseases is not the same for every variety of cancer," Lai said. "Obviously, having high levels of insulin does not promote health but perhaps such disorders can provide insight into the mechanisms of prostate cancer to help us learn how to eventually prevent prostate cancer."

Post-diagnosis weight change, body mass index, and breast cancer survival. Abstract no. B95:

Gaining weight following a diagnosis of invasive breast cancer could increase a woman's risk of death from the disease by more than half, according to researchers leading the Collaborative Women's Longevity Study. In fact, the researchers associated weight gain with a measurable increase in risk of death due to all causes, not just breast cancer.

"Our findings provide additional support for the benefits of maintaining a healthy weight and exercising," said Hazel B. Nichols, a doctoral student in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. "According to our results, there is a 14 percent increase in risk for every five kilograms -- about 11 pounds -- of weight gained."

To analyze the effect of weight gain on breast cancer survival, Nichols and her colleagues contacted women who had taken part in one of three previous studies begun in 1988 at sites in Wisconsin, Massachusetts and New Hampshire. Between 1998 and 2001, Nichols' team surveyed the women about post-diagnosis weight, weight gain, physical activity, diet and related items.

Of the original 4,021 breast cancer patients, the researchers identified 121 breast cancer-related deaths and 428 total deaths. For women classified as obese by body mass index - a measure of weight and height - the risk of dying from breast cancer was nearly 2.4 times that of women classified with a normal body weight. "Obesity was associated with risk of death even after accounting for age, menopausal status or smoking," Nichols said.

Nichols' study was funded by the Susan G. Komen for the Cure Breast Cancer Foundation.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In the press room (December 5-8):
215-409-4766

Chemoprevention, Naturally: Findings on Plant-derived Cancer Medicines

registration@aacr.org () — Thu, 06 Dec 2007 12:00:00 GMT

PHILADELPHIA - The next cancer-fighting therapeutic could be growing in your garden, according to research presented today, at the American Association for Cancer Research's Sixth Annual International Conference on Frontiers in Cancer Prevention Research, being held from December 5 to 8 in Philadelphia, Pennsylvania.

For example, a black raspberry-based gel might offer a means of stopping oral lesions from turning into a particularly dangerous and disfiguring form of cancer. And new studies show that cancer prevention might come in drinkable form: green tea extract, a powerful antioxidant, shows efficacy against colorectal cancer; and a new berry-rich beverage, made from a combination of known plant-based antioxidants, could prevent or slow the growth of prostate cancer.

Chemopreventative effects of a topically applied black raspberry gel on oral premalignant tumors. Abstract no. B35:

Oral squamous cell carcinoma is a deadly cancer that, even when treated successfully, often leaves patients permanently disfigured. Other than radical surgery, there are few known treatments. Researchers at Ohio State University, however, report a Phase I/II trial demonstrating that a gel made from black raspberries shows promise in preventing or slowing the malignant transformation of precancerous oral lesions.

"Black raspberries are full of anthocyanins, potent antioxidants that give the berries their rich, dark color, and our findings show these compounds have a role in silencing cancerous cells," said Susan Mallery, D.D.S., Ph.D., professor in the Department of Oral Maxillofacial Surgery and Pathology at Ohio State University's College of Dentistry. "This gel appears to be a valid means of delivering anthocyanins and other cancer-preventing compounds directly to precancerous cells, since it slowed or reduced lesion progression in about two-thirds of study participants."

According to American Cancer Society statistics, oral cancer is one of the deadliest of all cancers, with about 35,000 new cases each year in the United States and 7,500 deaths annually. These cancers generally begin as small, often unnoticed, lesions inside the mouth. "More than a third of untreated precancerous oral lesions will undergo malignant transformation into squamous cell cancer, but we do not have the capability to predict which lesions will progress," Mallery said.

The National Cancer Institute-funded trial included 30 participants, 20 of whom had identifiable precancerous lesions, and 10 normal controls. Each of the participants was instructed to gently dry the lesion sites (or a pre-selected control site for the normal participants) and rub the gel into the area four times a day, once after each meal and at bedtime.

After six weeks, about 35 percent of the trial participants' lesions showed an improvement in their microscopic diagnosis, while another 45 percent showed that their lesions had stabilized. About 20 percent showed an increase in their lesional microscopic diagnoses. Importantly, none of the participants experienced any side effects from the gel.

"The trial was designed to test the safety of the gel and detect any possible toxicity, but the next obvious step is a multicenter, double-blind, placebo-controlled Phase II study," Mallery said. "Such a study would enable us to determine that the black raspberries are the active factor and not just the gel base or the act of drying and rubbing the lesions."

The researchers also collected cell samples from the lesion sites of each participant before and after treatment in order to study the genetics and biology of the lesions. The majority of patients with precancerous lesions at the start of the trial showed elevated levels of COX-2 and iNOS, two proteins closely correlated with inflammation and malignant progression. Following treatment, Mallery says, levels of those proteins in the treated lesional epithelial cells decreased dramatically.

Mallery and her colleagues also examined samples for three tumor suppressor genes in order to determine what researchers call "loss of heterozygosity," whether or not a cancer cell has lost one of its two copies of the gene. Such loss greatly increases a cell's chances of losing the benefit of the tumor suppressor genes due to a second mutation or gene silencing event. Following the trial, the researchers noted that many lesions returned to normal, retaining both copies of each tumor suppressor gene. "We speculate that the chemopreventive compounds in black raspberries assist in modulating cell growth by promoting programmed cell death or terminal differentiation, two mechanisms that help "reeducate" precancerous cells," Mallery said.

"Oral cancer is a debilitating disease and there is a desperate need for early detection and management of precancerous lesions," Mallery said. "While screening can help detect the disease early - and survival rates are definitely improved the earlier the disease is caught - many of these precancerous lesions recur despite complete surgical removal. There are currently no effective chemopreventive treatments which could conceivably serve as either adjunctive or alternative approaches to surgery."

According to Mallery, the development of black raspberries as potential cancer-fighters is the result of decades of research into identification of naturally derived chemopreventive compounds by Ohio State researcher Gary D. Stoner, Ph.D., an emeritus professor at Ohio State University's College of Medicine and Public Health. Clinical studies stemming from his research are currently underway for oral, esophageal and colorectal cancer.

The gel looks deceptively like black raspberry jam, but it certainly does not taste like something you would want to spread on toast, Mallery says. The bioadhesive gel, which contains 10 percent freeze dried black raspberries, is devoid of many of the tasty sugars found in native berries.

The black raspberry gel was manufactured by the University of Kentucky's Good Manufacturing Production (GMP) facility. NanoMed Pharmaceuticals is partnering with OSU investigators Mallery, Stoner and Peter E. Larsen D.D.S. and Russell J. Mumper, Ph.D., of the University of North Carolina, in product development.

Suppressive effects of a phytochemical cocktail on prostate cancer growth in vitro and in vivo. Abstract no. A104:

A commercially available nutrition drink reduces the growth of tumors in a mouse model of human prostate cancer by 25 percent in two weeks, according to researchers from the University of Sydney. The drink, Blueberry Punch, is a mixture of plant-based chemicals - phytochemicals - known to have anti-cancer properties.

In particular, Blueberry Punch consists of a combination of fruit concentrates (blueberry, red grape, raspberry and elderberry), grape seed and skin extract, citrus skin extracts, green tea extract (EGCG), olive leaf and olive pulp extracts, tarragon, turmeric and ginger.

"We have undertaken efficacy studies on individual components of Blueberry Punch, such as curcumin, resveratrol and EGCG, in the same laboratory setting and found these effective in suppressing cell growth in culture," said Jas Singh, Ph.D., research fellow at the University of Sydney.

"While individual phytochemicals are successful in killing cancer cells, we reasoned that synergistic or additive effects are likely to be achieved when they are combined."

Singh and her colleagues studied the effect of the beverage on both cancer cell cultures and in mouse models that mimic human prostate cancer. After 72 hours of exposure to increasing concentrations of Blueberry Punch, prostate cancer cells showed a dose-dependent reduction in size and viability when compared with untreated cells, Singh says. After feeding mice a 10 percent solution of the punch for two weeks, the tumors in the test mice were 25 percent smaller than those found in mice that drank only tap water.

Because Blueberry Punch is a combination of several ingredients, it could have multiple mechanisms of action, Singh says. "Based on our initial findings, the mechanisms include, at least, the inhibition of the inflammation-related pathways, which is similar to the action of non-steroidal anti-inflammatory drugs; and inhibition of cyclin D1, which is similar to green tea action."

Based on these results, the researchers believe Blueberry Punch is now ready for human prostate cancer trials. Because Blueberry Punch is a food product rather than a drug, it is unlikely to have adverse reactions or side effects assuming that the individual is tolerant to all ingredients, Singh says. "The evidence we have provided suggests that this product could be therapeutic, although it requires clinical validation," Singh said.

The study was partially funded by the makers of Blueberry Punch, Dr. Red Nutraceuticals, a firm located near Brisbane, Australia, but the experiments were designed and conducted independently in the University of Sydney.

Inhibition of colorectal tumorigenesis in azoxymethane (AOM)-treated rats by green tea polyphenols. Abstract no. A134:

Elucidating a decade's worth of conflicting studies of the cancer-fighting benefits of green tea, researchers at Rutgers University have conclusively demonstrated that a standardized green tea polyphenol preparation can prevent the growth of colorectal tumors in a rat model of human colorectal cancer.

Results from previous studies using different tea constituents in this particular rat cancer model, which is thought to closely mimic human cancer, had been inconsistent. The researchers believe their findings will pave the way for clinical trials with green tea polyphenols in humans.

"Our findings show that rats fed a diet containing Polyphenon E, a standardized green tea polyphenol preparation, are less than half as likely to develop colon cancer," said Hang Xiao, Ph.D., research associate at the Department of Chemical Biology in Ernest Mario School of Pharmacy of Rutgers University.

According to Xiao, these results are consistent with previously published results by the project's primary investigator, C.S. Yang, Ph.D., professor and chair of the Department of Chemical Biology at Rutgers, which showed that green tea consumption was associated with lower colon cancer rates in Shanghai, China.

Xiao and his colleagues treated two groups of mice with azoxymethane (AOM), a widely used agent that has been shown to generate in rats colorectal tumors that share many characteristics with colorectal cancer in humans, Xiao says. They then split the rats into two groups that were each fed a high fat diet, which the researchers believe closely resembles a Western diet; half received a 0.24 percent solution of Polyphenon E. According to Xiao, the green tea extract contains four major polyphenols, the majority of which (about 65 percent) is EGCG, thought to be the main active ingredient.

"When you account for caloric consumption, 0.24 percent Polyphenon E in diet gave the experimental rats the equivalent of about four to six cups of tea a day," Xiao said. "While I can't make any recommendations for how much green tea people should drink each day, it isn't uncommon for some to drink that much tea."

After 34 weeks, rats that received Polyphenon E developed 55 percent fewer tumors compared to the control rats that did not receive Polyphenon E. Moreover, the tumors were 45 percent smaller in rats treated with green tea extract. Histopathological analysis by his colleague, Xinpei Hao, Ph.D., also showed that the treatment group had significantly lower incidence and number of malignant colon tumors. The researchers could also detect green tea polyphenols in the blood plasma as well as the colorectal mucosa of the rats who received the extract.

Meanwhile, the test rats weighed about five percent less than their control group counterparts, a result Xiao attributes to the ability of the green tea polyphenols to block lipid absorption in the body, which the researchers had previously demonstrated in a mouse model of obesity.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In the press room (December 5-8):
215-409-4766

Diet and Cancer Prevention: New Evidence for the Protective Effects of Fruits and Veggies

registration@aacr.org () — Thu, 06 Dec 2007 12:00:00 GMT

PHILADELPHIA -- The age-old refrain, "Eat your vegetables!" gets scientific support as researchers present the latest findings on cancer prevention at the American Association for Cancer Research's Sixth Annual International Conference on Frontiers in Cancer Prevention, being held December 5 - 8 in Philadelphia, Pennsylvania.

Today, researchers present new data that demonstrate how diets full of raw vegetables -- particularly broccoli sprouts -- and black raspberries could prevent or slow the growth of some common forms of cancer.

Dietary administration of black raspberries modulates markers of oxidative stress in patients with Barrett's esophagus. Abstract no. B34

Black raspberries may protect against esophageal cancer by reducing oxidative stress in patients with Barrett's esophagus (BE), a pre-cancerous condition that usually arises due to gastroesophageal reflux disease, report researchers at The Ohio State University.

According to the researchers, BE patients have a 30- to 40-fold increased risk of developing esophageal adenocarcinoma (EAC), the fastest growing cancer in terms of incidence in the United States. EAC is a deadly cancer with a 15 percent five-year survival rate; an estimated 14,000 people will die from esophageal cancer in the U.S. in 2007. Moreover, a number of treatment options are available to BE patients for symptom relief, researchers say, but none has proven curative or eliminated the risk of cancer progression.

"In addition to gastroesophageal reflux disease, increasing body mass index or body fatness is strongly associated with EAC development; whereas, plant-based diets and particularly increased fruit consumption has been associated with decreased risk for EAC," said Laura A. Kresty, Ph.D., assistant professor of at Ohio State University.

According to Kresty, research using animal models of BE showed that black raspberries inhibited chemically induced oral, esophageal and colon cancers. The studies showed that berries reduced measures of oxidative stress (the destruction done to cells by oxygen ions or small reactive molecules containing oxygen), decreased DNA damage, inhibited cellular proliferation rates, and reduced the number of pre-cancerous cells in the esophagus and colon.

"We can give black raspberries before we have any initiated cells, or we can administer after we already know we have initiated cells," Kresty said. "What's promising about the berries is that they work in both cases, and in multiple models. There aren't nearly as many agents that work in the latter scenario."

In this study, BE patients ate 32 or 45 grams (female and male, respectively) of freeze-dried black raspberries daily for 26 weeks. After 26 weeks, patients experienced a statistically significantly decline in the mean urinary levels of 8-Isoprostane, an indicator of global oxidative stress and DNA damage -- both processes linked to the development of BE and EAC. According to Kresty, 58 percent of patients experienced marked individual level declines of 8-Isoprostane. Among 37 percent of BE patients, the black raspberry regimen also resulted in the increased expression of tissue levels of GSTpi. GSTpi is an enzyme that detoxifies carcinogens and reactive oxidants and is typically reduced in Barrett's epithelium compared to normal esophageal epithelium.

"Black raspberries have a good profile in terms of tolerability -- many of the potential toxic side effects associated with a new drug are less of an issue because we are simply administering a food in a non-traditional manner," Kresty said. "Patients seem amenable to such an approach, they understand it and enjoy being able take positive action for potential health gains."

Inhibition of urinary bladder carcinogenesis by broccoli sprouts. Abstract no. B149:

Your mom was right when she told you to eat your broccoli, or at least your broccoli sprouts. Researchers have found that this rich source of isothiocyanates (ITCs) -- a well-known class of cancer prevention agents -- could play a direct role in preventing bladder cancer.

"The bladder is like a storage bag, and cancers in the bladder occur almost entirely along the inner surface, the epithelium, that faces the urine, presumably because this tissue is assaulted all the time by noxious materials in the urine," said senior author Yuesheng Zhang, M.D., Ph.D, professor of oncology at Roswell Park Cancer Institute. "The ITCs in broccoli sprout extracts after oral ingestion are selectively delivered to the bladder epithelium through urine excretion."

Using a rat model of bladder cancer, Zhang and his colleagues found that freeze-dried aqueous extract of broccoli sprouts significantly, and dose-dependently, inhibited bladder cancer development. The incidence, multiplicity, size and progression of bladder cancer were all inhibited by the extract, while the extract itself caused no observable changes in the bladder. This protective effect of the extracts was associated with a significant increase in the bladder of several enzymes that are known to protect against oxidants and carcinogens, Zhang says.

In the body, ITCs are metabolized to dithiocarbamates (DTCs). The researchers measured the levels of ITCs and DTCs in the blood, tissue and urine of the rats fed with the extracts. More than 70 percent of the ITCs present in the extracts were excreted into the urine as ITC equivalents (ITCs + DTCs) in 12 hours after a single oral dose, indicating high bioavailability and rapid urinary excretion.

What is more striking, Zhang says, is that the concentrations of ITC equivalents in the urine of extracts-treated rats were two to three orders of magnitude higher than those in plasma, indicating that the bladder epithelium is most exposed to orally dosed ITCs. Indeed, tissue levels of ITC equivalents in the bladder were significantly higher than in the liver, demonstrating that the ITCs in the extracts are efficiently and selectively delivered to the bladder epithelium through urinary excretion, Zhang concludes.

Consumption of raw, but not cooked, cruciferous vegetables and reduction of bladder cancer risk. Abstract no. B47:

While researchers have long known that cruciferous vegetables are chock full of isothiocyanates (ITCs), which are a well-known class of cancer prevention agents especially promising in bladder cancer chemoprevention, they didn't know how much one needed to eat to reap the protective benefits.

Researchers from Roswell Park Cancer Institute report that three or more servings a month of raw cruciferous vegetables like broccoli, cabbage and cauliflower, may reduce bladder cancer risk by approximately 40 percent, overall.

The Roswell Park team surveyed the dietary habits of 275 individuals with incident, primary bladder cancer and 825 individuals without cancer. The researchers surveyed patients about their pre-diagnostic intake of raw and cooked cruciferous vegetables, their smoking habits and other cancer risk factors. They observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable consumption. When compared to smokers who ate less than three servings of raw vegetables, non-smokers who ate at least three servings a month were almost 73 percent less likely to develop bladder cancer, the researchers say.

A key factor in the research was that it's a survey of raw cruciferous vegetables. Previous research had surveyed intake of any cruciferous vegetables -- cooked or not -- and results proved inconsistent. Cooking significantly reduces the availability of ITCs for absorption into the body, according to researchers.

"Cooking can reduce 60 to 90 percent of ITCs," says Li Tang, M.D., Ph.D. of Roswell Park Cancer Institute and lead researcher on this study. "Heating destroys the enzyme that converts the precursor glucosinolates into ITCs, and also destroys ITCs already formed, which is why you need to eat raw cruciferous vegetables to receive the food's maximum benefit."

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In the press room (December 5-8):
215-409-4766

Public Health and Cancer Prevention: Success and Future Challenges in Cancer Policy

registration@aacr.org () — Thu, 06 Dec 2007 12:00:00 GMT

PHILADELPHIA - Medical research has revealed much about cancer prevention, but is the information reaching all Americans, and are they acting on it? Today, at the American Association for Cancer Research's Sixth Annual International Conference on Frontiers in Cancer Prevention Research, being held from December 5 to 8 in Philadelphia, Pennsylvania, researchers explore the question of how best to translate cancer prevention science into public health policy.

Quitting smoking and inoculation with the human papillomavirus (HPV) vaccine are two ways that major segments of the general population can drastically lower their risk of developing certain cancers, yet researchers have found that these messages are not necessarily translating into action by the public.

Policies to reduce tobacco harm: What works? Abstract no. A29

To discourage cigarette use, the strategies that are working best on a global basis are to use large graphic package warning labels, ban cigarette advertising, institute smoke-free policies, increase cigarette prices and implement methods to prevent smuggling and counterfeiting of tobacco products, say researchers at Roswell Park Cancer Institute involved in an International Tobacco Control (ITC) Policy Evaluation study. What hasn't worked as well as hoped is mandating tar and nicotine levels in cigarettes, they add.

The researchers have been investigating progress on controlling tobacco use from the ongoing Framework Convention on Tobacco Control (FCTC), the treaty devoted to improving public health put forth by the World Health Organization.

The FCTC was adopted by WHO's member states in May, 2003, and became legally binding for those countries that ratified the treaty in 2005. To date, 151 countries have done so, and are thus required to implement the policies within three years.

"For the first time ever, we are beginning to scientifically assess which governmental tobacco control policies are working and which ones are not," said K. Michael Cummings, Ph.D., MPH, chair of the Department of Health Behavior at Roswell Park Cancer Institute. "In the same way that evidence-based medicine has been built from rigorous evaluation of treatment options, our goal is to contribute to the development of a sound science base for tobacco control policies."

The ITC serves to study which policies are working best in countries that have imposed restrictions, says Cummings. Cummings started the study in four countries in 2002 with a $1.5 million grant from the Robert Woods Johnson Foundation, and to date, $35 million has been raised to expand the research into 15 countries, utilizing the aid of 60 investigators from 17 research institutes.

Because randomized clinical trials can't be used to evaluate government policies, the ITC study uses as controls those countries that have implemented tobacco control policies and compares the effects on tobacco use behaviors in countries that have not, such as the United States. It is tracking tobacco use behaviors of 1,000 to 2,000 participants in each of the countries, Cummings says. "This is a new model for global public health research that can be used to evaluate other public health policies such as HIV, diet, and cancer screening," he said.

"It made sense for WHO to start off with tobacco as a focal point for action since tobacco use is the leading cause of preventable death in the world today and is a growing epidemic in the developing world," he said. Tobacco use was responsible for 100 million deaths in the 20th century, and that number is expected to grow to 1 billion in the 21st century, he says.

ITC researchers have found that boosting tobacco taxes, comprehensive advertising bans, smoke-free laws, and strengthening cigarette package warnings is an effective recipe for reducing tobacco consumption. "Our research on package warnings has revealed that these warnings, especially if they are large and graphic, are more effective than anyone realized, especially in poorer countries that can't afford expensive counter-marketing campaigns," he said.

An example of a policy that hasn't worked, Cummings says, is the European Union's (EU) establishment of maximum emission standards for tar and nicotine. The goal was to make cigarettes less toxic, but the testing method adopted by the EU was flawed and cigarette makers increased filter ventilation to get around the new rules. Actual exposure to toxins didn't change. "The well intentioned, but flawed EU policy has given smokers the false illusion that their cigarettes deliver less tar and nicotine, when they don't," he said.

The ITC has also established the first international cigarette repository, which currently holds 10,000 cigarette pack varieties from 15 different countries. This research shows that tobacco manufacturers alter their products frequently without revealing that they are doing so, he says. "Foods and drugs are regulated so that consumers are informed when the products are altered. The same should be true for tobacco products," Cummings said.

Physician Intentions and HPV Vaccination: The First Year. Abstract no. A104

Before last summer, when the FDA approved use of the first vaccine developed to prevent cervical cancer, 92 percent of several hundred family care physicians surveyed in the poorer urban areas of metropolitan New York City said they would recommend the vaccine to their young female patients. But over a year later, only 10 percent of these same physicians had actually vaccinated some of their patients, report researchers at Columbia University.

While vaccines usually take time to come into widespread use, a delay in use of this proven cancer preventative will result in lost opportunity for many young women, says the study's lead investigator. Sherri Sheinfeld Gorin, Ph.D., a senior member of the Herbert Irving Comprehensive Cancer Center and Associate Professor of Health Behavior.

"Routine use of the vaccine will play out over time, but how many women will be deprived in the intervening years?" she said. "Physician recommendation is key to vaccination, and these findings suggest there is a critical need for strategies that encourage physicians to follow through on their own good intentions."

The study first sampled 235 multi-ethnic/racial urban primary care physicians with a questionnaire in early 2006 to see if these doctors intended to discuss use of the human papilloma virus (HPV) vaccine, when approved, with their young female patients. "It's important to know if physicians plan to educate their patients about HPV prevention, because fewer than one-third of the population has heard of HPV," Sheinfeld Gorin said.

They found that 92 percent of the physicians were extremely or somewhat likely to use the vaccine and that doctors who routinely offer pelvic examinations for their female patients, who are more familiar with the professional guidelines for cervical cancer screening, and who are female, were most likely to offer the vaccine.

But a follow-up audit of a proportion of patient charts in these practices, conducted between 12-18 months after the vaccine was approved, found that only 10 percent had vaccinated eligible young patients. By contextual comparison, 14 percent of patients received the hepatitis B vaccine in 1991, about one year after it was approved for universal use among infants.

Sheinfeld Gorin says she has some clues as to why so few physicians actually used the vaccine once it was approved. One is cost: even though the vaccine's $360 price tag is usually reimbursed by insurance, physicians have to pay for their vaccine stocks up front, they have to store them and make sure they don't expire. "That is a financial burden some physicians don't want to have until use of the vaccine becomes more commonplace," she said.

Another is that physicians may not have had a chance yet to discuss the vaccine with their young patients. But the most likely scenario, based on other studies, is that physicians presume patients will not be accepting of an HPV vaccine, Sheinfeld Gorin says. "So they don't talk about it yet, and expect that social acceptance will improve in the future," she said. "But, in fact, research has shown that patients are quite responsive to the vaccine. That's why we need a strategy now to help physicians discuss HPV vaccines with their patients."

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In the press room (December 5-8):
215-409-4766

AACR Introduces Cancer Prevention Research, a New Journal Devoted Exclusively to the Growing Science of Cancer Prevention

registration@aacr.org () — Tue, 04 Dec 2007 12:00:00 GMT

Researchers: Call for Papers

PHILADELPHIA - In response to the growing body of research in the field of cancer prevention, the American Association for Cancer Research (AACR) announces the launch of a major peer-reviewed scientific journal, Cancer Prevention Research, and invites submissions of papers. This important new journal is the first in the world dedicated exclusively to cancer prevention, from preclinical research to clinical trials.

"In the past, scientists and interested readers have had to parse cancer prevention articles from many other journals, unable to find the full range of prevention research and opinion in one resource," said Editor-in-Chief Scott M. Lippman, M.D., professor at The University of Texas M. D. Anderson Cancer Center. "The richness and scope of our field now parallel those of mainstream oncology and require this new, centralized home for the wide-ranging literature that supports prevention discovery."

"The main purpose of Cancer Prevention Research is to build a translational bridge between the basic and clinical sciences in the field of cancer prevention," said Lippman. Articles will cover the preclinical and clinical work of nearly every cancer prevention discipline, from molecular biology to medical oncology, from behavioral science to surgical oncology, from nutritional science to exciting new areas such as infection- and inflammation-related cancer prevention. "Cancer Prevention Research also will serve as a forum for perspectives on key public policy issues affecting cancer prevention and will highlight the central role of cancer prevention and early detection in public health," Lippman said.

"The emphasis on linking preclinical and clinical research in prevention is unique among scientific journals. The idea to launch Cancer Prevention Research came from the basic, clinical and translational researchers who are AACR members," said AACR President William N. Hait, M.D., Ph.D. "On behalf of AACR, I thank Dr. Lippman and his outstanding team of editors and staff who have devoted their time and expertise to launching this important new vehicle for scientific discovery in a field that holds tremendous potential for saving lives."

"This new journal will join our established interdisciplinary journal, Cancer Epidemiology, Biomarkers & Prevention, and our annual Frontiers in Cancer Prevention Research meeting as part of the AACR's comprehensive approach to cancer prevention," Hait added.

Scientific articles published in Cancer Prevention Research will fall into four primary research categories, each with a unique role in the study of cancer prevention: oncogenesis, intervention, risk assessment and early detection. Oncogenesis studies include those that cover the origins of cancer development and the cellular mechanisms that could prevent cancer growth. In addition to translational clinical studies, intervention articles will include, for example, preclinical studies on the molecular mechanisms of potential preventative agents or animal studies of new preventive drugs or nutritional interventions. According to Lippman, the field is trending strongly toward these types of preclinical studies to validate rationales before launching definitive randomized controlled clinical trials in humans.

The sections on risk assessment and early detection research will include work in presymptomatic disease to prevent the clinical consequences of cancer. Through articles on leading-edge molecular biomarker research, these sections will join the identification of high cancer risk with very early detection of cancer. "These sections also will highlight the growing interface between cancer prevention and cancer therapy and the emphasis of Cancer Prevention Research on communicating discoveries that cross the gap between the basic and clinical sciences of cancer prevention," Lippman said.

This announcement and call for papers coincides with the AACR's Sixth Annual International Conference on Frontiers in Cancer Prevention Research, being held December 5 to 8 in Philadelphia, Pennsylvania, a scientific meeting that features the latest biological, medical and behavioral research behind cancer prevention.

Beginning in March, 2008, Cancer Prevention Research articles will be published continually online as soon as edited and will be open to anyone during the introductory phase. Regular monthly issues will begin appearing in June 2008.

For further information and to submit a paper, click here.

Deputy Editors of Cancer Prevention Research are Cory Abate-Shen, Ph.D.; Powel H. Brown M.D., Ph.D.; Raymond N. DuBois, M.D., Ph.D.; Ernest T. Hawk, M.D.; Caryn Lerman, Ph.D.; Thea Tlsty, Ph.D. and Janet Woodcock, M.D. Senior Editors are Monica M. Bertagnolli, M.D.; Martin J. Blaser, M.D.; Andrew J. Dannenberg, M.D.; Paul F. Engstrom, M.D.; Judy E. Garber, M.D.; Jean-Pierre Issa, M.D.; Jonathan M. Kurie, M.D.; Lawrence J. Marnett, Ph.D.; Lynn M. Matrisian, Ph.D.; William G. Nelson, V, M.D., Ph.D.; Brian J. Reid, M.D., Ph.D.; David Sidransky, M.D., Ph.D.; Eva Szabo, M.D.; Mark Taketo, M.D., Ph.D.; Brent M. Vose, Ph.D. and Eileen P. White, Ph.D. Statistical Editors are J. Jack Lee, Ph.D., D.D.S. and Susan G. Hilsenbeck, Ph.D.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org

Genetic and Behavioral Differences Add to Prostate Cancer Disparities

registration@aacr.org () — Thu, 29 Nov 2007 12:00:00 GMT

ATLANTA - African-American men face an observable disadvantage versus Caucasian men when it comes to prostate cancer survival. Not only is prostate cancer detected later in African-Americans, it is often more aggressive and harder to treat.

Findings on the social and biological factors influencing disparities among African-American men are reported today at the American Association for Cancer Research conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, being held November 27-30 in Atlanta. New research on the effects of weight, genetics and even religious beliefs on prostate cancer are among the day's highlights.

An exploratory investigation of prostate cancer knowledge, cultural beliefs, and values among black men of West African ancestry, Abstract no. A-3:

A survey of African-American and Nigerian men shows that African-American men are more fatalistic in their cancer beliefs and less likely to exhibit religious coping skills, according to a team of researchers based at Florida A&M University and H. Lee Moffitt Cancer Center.

Among all American ethnic groups, African-American men tend to suffer disproportionately from aggressive prostate cancer, which is often detected at a much later stage. This survey provides a baseline of African-American cultural beliefs and values toward prostate cancer that might serve in crafting prostate cancer awareness programs, the researchers say.

"Men who have fatalistic beliefs about prostate cancer, for example, may be less likely to take the steps necessary to prevent cancer or undergo cancer screening to detect cancer," said lead researcher, Folakemi T. Odedina, Ph.D., professor and director of Florida A&M's Economic, Social & Administrative Pharmacy program. "These are cultural beliefs that compound existing health disparities for African-American men, and we must understand these beliefs if we are to understand how to change behavior."

The study is the first to compare cultural knowledge and beliefs among African-American, indigenous West African and West African immigrant men in an attempt to uncover the cultural components of the prostate cancer disparity. According to Odedina, both Nigerian men and West African immigrants to the United States are reported to have a lower incidence of prostate cancer than African-Americans, although some studies conflict regarding the magnitude of this difference.

The survey, conducted by Odedina and her colleagues in the United States and Nigeria, gauged the attitudes of African-American men, Nigerian men, and Nigerian men who have moved to the United States.

"We decided to understand prostate cancer health disparities in African-American men by separating environmental and psycho-social factors from genetics," Odedina said. "Since the Trans-Atlantic slave trade took so many men from West Africa - more than a third of slaves came from the Nigeria region, alone - African-American and West African men have similar genetic backgrounds, but much cultural dissimilarity."

Odedina and her colleagues surveyed 81 African-American men from Orlando, Florida; 121 Nigerian immigrants living in Houston, Texas; and 128 men in Abeokuta, Nigeria. The survey explored cultural beliefs thought to impact cancer survival, such as cancer fatalism, religious coping (the ability to use faith to help manage disease treatment), temporal orientation (a measure of an individual's focus on the past, present or future) and acculturation (the degree to which an individual from a non-dominant culture takes on the behavior and trappings of the dominant culture).

Among their findings, the researchers say that while African-American men may know more about prostate cancer, they are less likely to possess cultural beliefs and values that could improve cancer detection and control. In contrast to Nigerian men, African-American men are 22 percent more likely to hold fatalistic beliefs about cancer and 60 percent less likely to possess the religious coping skills that could sustain them through cancer therapy, Odedina says. Among African-American men and women, fatalistic perspectives have also been reported to affect cervical cancer, breast cancer, colorectal cancer and fecal occult blood testing, she says.

Although the impact of religion and spiritualism on cancer prevention or detection has not been well documented in the literature, it has been suggested that it may deter women from seeking treatment for breast cancer, Odedina says.

Association between PSA and leptin, adiponectin, HbA1c, or C-peptide among African-American and Caucasian men. Abstract No. A-33:

Obesity and diabetes might mask the onset of prostate cancer in African-American men, making it difficult to detect early-stage and treatable prostate cancer in a population of men already prone to aggressive cancer, according to researchers at Vanderbilt University. Their findings examine the link between prostate-specific antigen (PSA) - a blood marker which at elevated levels indicates the presence of prostate cancer - and biological markers for obesity and diabetes.

"African-American men, among all racial groups, are more likely to be diagnosed with prostate cancer at an advanced stage and are also more likely to die from prostate cancer," said Jay H. Fowke, Ph.D., M.P.H., an assistant professor of Medicine and cancer epidemiologist at Vanderbilt-Ingram Cancer Center.

According to Fowke, obese men are also more likely to present with prostate cancer at an advanced stage. Most prostate cancer is diagnosed in response to a PSA test, and a high body mass index (BMI) often corresponds with lower blood PSA levels.

"Diabetes and metabolic disturbances associated with insulin regulation are more common among African-Americans compared to Caucasians, and metabolic disorders associated with obesity and diabetes may lower PSA levels and may cause a delay in referring a patient for a biopsy," Fowke said. "This may be in part why we often don't detect prostate cancer in African-American men until it is already fairly advanced."

Given the increasing rates of obesity and diabetes among African-Americans, Fowke and his colleagues sought a better understanding of the relationship between race, metabolic disorders and PSA levels used to detect early-stage prostate cancer.

The researchers examined participants in the Southern Community Cohort Study, a National Cancer Institute-funded initiative that monitors the health of 90,000 men and women between the ages of 40 and 79 throughout the southern United States. The researchers randomly selected 121 African-American men and 121 Caucasian men; each group had the same proportion of obese and overweight men, as determined by their BMI. Study participants had no prior diagnosis of cancer or diabetes.

From each participant's blood sample, the researchers compared PSA levels with the amounts of HbA1c, C-peptide, leptin and adiponectin - naturally occurring blood-borne molecules that have a biological role in metabolism, insulin activity, or the function of fat cells. Among African-Americans, PSA levels were 50 percent lower among men with higher levels of C-peptide, a biomarker that reliably indicates an increase in insulin. This association was especially prevalent among obese African-American men, Fowke says. PSA levels also declined somewhat among obese Caucasian men with high C-peptide levels, but this relationship was not as strong as it was in the African-American group.

The researchers saw a similar pattern in Caucasian men regarding the diabetes biomarker HbA1c, where PSA levels were 50 percent lower among men with higher levels of HbA1c. PSA levels were not associated with HbA1c in the African-American group, perhaps suggesting that there may be differences between Caucasian and African-American men in the way PSA responds to obesity.

"There are a number of complex components related to obesity and insulin activity, and we are seeing that metabolic disturbances can have an effect on PSA levels," Fowke said. "It doesn't invalidate PSA screenings, but it does demonstrate that we need research to better understand how obesity and diabetes may be affecting our ability to detect early-stage prostate cancer among African-American men at high-risk for advanced prostate cancer."

Potential role for nuclear matrix proteins hnRNPH1 and SAFB-2 in ethnic disparity of prostate cancer, Abstract no. B-99:

Researchers based at Tulane University report the discovery of biological markers of prostate cancer which are involved in the growth of tumor cells, shedding light on the genetic basis for the prostate cancer burden faced by African-American men.

In prostate tumors samples taken from African-American and Caucasian men, the researchers found that two proteins are overproduced in 90 percent of tumor cells from the African-Americans studied. These structural proteins, called hnRNP-H1 and SAFB-2, in part comprise the nuclear matrix, the mesh of molecules that serves as the supporting "skeleton" of the cell's nucleus.

"We have employed a unique functional genomics approach to unravel the molecular mechanisms underlying the disproportionate incidence and mortality among African-American men," said Asim B. Abdel-Mageed, D.V.M, Ph.D., associate professor and director of the Molecular Oncology Research program in the Department of Urology at Tulane University School of Medicine.

Currently, prostate specific antigen (PSA) and digital rectal examinations are the two most common methods of detecting prostate cancer. African Americans are typically diagnosed with prostate cancer more frequently and later - when the cancer is at an advanced stage and more aggressive - than any other ethnic group in the United States. According to Abdel-Mageed, earlier detection of prostate cancer might decrease this health disparity. "The target genes may have potential clinical utility as biomarkers or prognostic indicators of disease progression in African-American men independent of a PSA screen," Abdel-Mageed said.

With funding from the National Cancer Institute and American Cancer Society, the researchers compared prostate cancer cells from 50 African-American and Caucasian men, aged 50 to 60, matched so that each group comprised similar tumor grades. Using DNA sequencing and screening techniques to determine the genetic activity of these tumor cells, the researchers demonstrated the increased production of heterogeneous nuclear ribonucleoprotein H1 (hnRNP-H1) and scaffold attachment factor B2 (SAFB-2) in African-American men as opposed to Caucasians.

In addition to their role as potential blood-borne biomarkers for disease screening, the researchers are excited by the role these proteins play in chemical pathways that control disease progression. "Both of these genes share many structural and functional similarities, including possession of messenger RNA binding sites that could allow them to regulate how other genes are read from the DNA," said Abdel-Mageed.

Through related means, Abdel-Mageed says, these proteins are somehow involved in the relationship between hormones and prostate cancer progression. The researchers determined that hnRNP-H1 protein, in particular, binds to and activates the androgen receptor (AR), a nuclear protein that serves as an intermediate that allows male hormones from the bloodstream, such as testosterone, to activate genes encoded in the DNA. Testosterone and other hormones have been shown to influence prostate cancer growth, Abdel-Mageed says.

"Similarly, SAFB-2 was shown to have a role in regulation of hormone-related genes. "Based on these data, we believe their selective expression may represent a novel a mechanism for disease progression and development of hormone refractory disease in African Americans," said Abdel-Mageed.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; healthcare professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
(267) 646-0554
greg.lester@aacr.org
In Atlanta (November 27-30):
(404) 586-6124

It Takes a Community to Address Cancer Disparities among Underserved Minority Populations

registration@aacr.org () — Thu, 29 Nov 2007 12:00:00 GMT

ATLANTA - Cancer affects whole communities of people with similar genetic heritage and cultural behaviors, yet medical researchers often have trouble uncovering data on minority populations and promoting changes that could improve health. That is why many researchers have begun to collaborate directly with community groups. Such associations can improve the quality of data collection; provide needed insight into social factors involving help; and lead to sustained health improvements among disadvantaged populations.

Today in Atlanta, researchers report the results of successful initiatives begun in Nashville and among the Navajo Nation at the American Association for Cancer Research conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, being held November 27-30. Their community research projects are helping African-Americans to stop smoking, Hispanic immigrants to meet their basic cancer care needs and members of the Navajo Nation to educate a dramatically underserved population about colorectal cancer.

Hispanic Health in Nashville 2007: Cancer Needs Assessment, Abstract no. B-43:

Like many communities in the United States, Nashville, Tennessee, has over the past two decades experienced an unprecedented influx of immigrant Hispanics - a population whose healthcare needs are understudied and not well documented in the academic literature. In response, a coalition of Nashville-area researchers have teamed with community groups to survey the cancer care and prevention needs of Hispanic immigrants. Their findings will help shape future community programs and potentially reduce the burden of cancer among local Hispanics.

"Our local Hispanic community has grown nearly seven-fold over the last decade, yet we do not know much, if anything, about their cancer-related needs," said lead investigator Pamela Hull, Ph.D., associate director of the Center for Health Research at Tennessee State University. "Our survey has found that members of the Nashville Hispanic community are overwhelmingly interested in cancer prevention and healthcare efforts - including cancer clinical trials and cervical cancer vaccination - yet the community generally lacks access to care and information."

Since 1990, the Nashville Hispanic population has grown from a mere handful to nearly 40,000 people, according to census data, but the real figure might be higher, says Hull. "Over the last 15 years or so, many smaller cities and rural communities across the interior of the United States have seen a similar growth of Hispanic immigrants moving from the states with traditionally larger Hispanic populations," Hull said. "Our survey, and the participatory methods we use, could help inform these new growth communities about their blossoming Hispanic populations. Statistics on the health of Hispanic immigrants in Tennessee practically do not exist, which is especially worrisome given the lack of health insurance among this population."

The survey was conducted by the Cancer Outreach Core of the Cancer Disparities Partnership, collaboration between Meharry Medical College, Vanderbilt University, and Tennessee State University, with funding from the National Cancer Institute.

According to the American Cancer Society, Hispanics, in general, face lower rates of cancer than Caucasians, but higher rates for certain types of cancer, such as cervical, stomach, liver and leukemia. Hispanics also have lower survival rates for most cancers. However, cancer rates may differ according to a person's country of origin, Hull says.

Hull and her colleagues began a community-based participatory approach to survey the needs of the Hispanic population by partnering with the Progreso Community Center - a grassroots Hispanic community organization - and the Nashville Latino Health Coalition. Together, they trained Hispanic community members and bilingual students to collect data in neighborhoods and public venues across the Nashville area.

They interviewed over 500 Hispanics in the urban area, with an average age of 35. According to their results, 98 percent of respondents were not born in the United States, with more than half emigrating from Mexico. On the surface, Hull says, some of the results of the survey may seem bleak - 80 percent of those surveyed lack health insurance, two-thirds lacked high school degrees and 55 percent spoke little or no English.

The researchers found, however, that Nashville Hispanics took a great interest in cancer care and prevention. Cancer was rated as the top health concern out of a list of 25 topics. Nearly 75 percent indicated they wanted to learn more about cancer prevention, and just over half wanted more information on cancer screening. The vast majority of participants said they would participate in a clinical trial to receive treatment if they had cancer. Participants with daughters under age 18 were asked if they would obtain the new human papillomavirus vaccine for their daughters if it were free, and more than 90 percent said they probably or definitely would.

"The good news is that this population places a strong emphasis on prevention and is receptive to cancer education and screening," Hull said. "With this baseline information, we will continue to work with Progreso Community Center and Nashville Latino Health Coalition - with direct involvement of grassroots Hispanic community members - to develop culturally appropriate programs and further research to address the cancer-related needs of Hispanics."

Nashville NAACP tobacco prevention initiative: An example of community-based participatory action research, Abstract no. B-42:

When Reverend Raymond Bowman, pastor of Spruce Street Baptist Church in Nashville, Tennessee, brought his concerns about smoking in the African-American community to members of the local branch of the National Association for the Advancement of Colored People, little did he know that he would start something of a revolution in local community cancer prevention.

Although it just began in 2006, the Nashville NAACP Tobacco Prevention Initiative has increased awareness of the dangers of tobacco use, begun changing smoking behavior and tobacco-related policy and provided researchers with valuable epidemiological data on public health disparities in the African-American community.

"The lesson we have learned is that change is possible when academic health research focuses on the community in ways that are compatible with culture and social context," said initiative leader Elizabeth Williams, Ph.D., associate director of minority affairs at Vanderbilt University's Vanderbilt-Ingram Cancer Center.

Researchers call this a Community-based Participatory Action Research (CBPAR) methodology, one that engages participants as partners, not just as research subjects. The initiative partners - local community leaders, researchers and students from local universities and medical centers - believe the initiative serves as a role model for similar efforts among minority populations across the country.

African-Americans use tobacco differently than other Americans, Williams says, which illustrates the unique needs of this particular community. African-American women, for example, tend to start smoking later in life than Caucasian women do, and are much less successful when trying to quit. Menthol cigarettes, which are often marketed to African-Americans, may contribute to the increased use of tobacco and cancer disparities among this population as well, Williams says. "Studies have shown that African-Americans may even smoke fewer cigarettes, but that it affects them disproportionately in cancer incidence and mortality," she said.

According to Williams, tobacco use, among all the behavioral factors that lead to cancer, is a key target of cancer prevention efforts. "Cancer affects African-Americans differently than it does Caucasians and other ethnic groups," Williams said. "The disease is more severe and it is often detected at an advanced stage, when treatment is more difficult or fewer options are available."

The CBPAR approach allows Williams and her colleagues to strategize about ways to address tobacco use and chronicle the development of the initiative through qualitative methods including participant observation, focus group data, key informant interviews and historical archives. Since its inception last year, the initiative has successfully changed local policies about smoking on church property and developed community-based tobacco prevention activities, such as a 2006 Kick Butts Community Forum and a 2007 World No Tobacco Day Event. Initiative members take part in service-learning projects, which include assessing the needs of and tailoring programs for nearly 7,000 members of the more than 20 churches active in the program.

Nashville is firmly in the Bible Belt of the United States, Williams says, and the connection between church and community provides researchers with a vital avenue for preventing tobacco use.

"Our work involves an active process for change - the community might not listen to public service announcements, but they will listen to pastors, friends and family members who speak out about their cancer experiences," Williams said. "Beyond listening, they are motivated to act on behalf of their health. When that happens, addressing cancer disparities moves from rhetoric to action."

Colorectal Cancer Screening Knowledge and Awareness on the Navajo Reservation, Abstract no. B-38

Some minority populations in the United States are so isolated from mainstream cancer awareness efforts, they seem like separate nations unto themselves - a literal distinction for Navajo Indians. In the first-ever assessment of cancer awareness among members of the Navajo Nation, researchers at the University of Arizona Cancer Center have determined that cancer education efforts have not reached the tribe, particularly with regard to colorectal cancer (CRC).

With funding from the National Cancer Institute, the study leader, Priscilla Sanderson, Ph.D., a post-doctoral fellow at the University of Arizona Cancer Center and herself a Navajo, has undertaken an extensive review of attitudes toward cancer among the nearly 200,000 members of the Navajo Nation who live in the Navajo Reservation, an area of land that occupies most of northeastern Arizona as well as parts of New Mexico and Utah.

To establish a baseline of colorectal cancer awareness, Sanderson surveyed Navajo at tribal fairs and health centers and held focus groups of tribal elders. "Results of our studies show that awareness and interest in colorectal rectal cancer screening among the Navajo Nation is present," Sanderson said. "However, the proportion of those reporting undergoing CRC screening is much lower than the national average, and that may have a direct effect upon cancer survival."

Colorectal cancer is one of the most common forms of cancer in the United States, with over 150,000 new cases of CRC each year. Since CRC is most common in older adults, doctors generally recommend that every man and woman be regularly screened after age 50. If caught early, CRC has a 50 percent five-year survival rate. According to Sanderson, hard data on CRC incidence among Navajo is not conclusive, but rates are actually thought to be somewhat lower than in other ethnic groups in the United States.

"Part of the problem involves public health resources, but there is a definite cultural component that has inadvertently stood in the way of cancer awareness," Sanderson said.

One example given by Sanderson is that many Navajo - especially the older members of the tribe - do not speak English as a primary language. In surveying elder tribal members, Sanderson found that 47 percent spoke only Navajo, while none spoke English as a primary language.

The fact that the Navajo language lacks a specific word for cancer might be a conceptual barrier for some, Sanderson says. When discussing cancer, Navajo typically use the phrase, "Lood doo náziihii," which literally means "the sore/wound that does not heal." "It is difficult to assess a person's understanding of cancer if you lack a common vocabulary," Sanderson said.

While the study's ongoing surveys and focus groups have not yet captured the entire picture of CRC awareness among the Navajo Nation, Sanderson believes the information she has developed so far can serve as a baseline by which to judge future efforts in raising cancer awareness. At two annual tribal festivals on the Navajo Reservation, only 16 percent of survey respondents, who were typically women in their forties, had reported ever having been screened for CRC. Surveys conducted at two Indian Health Service hospitals in 2007, however, showed that while 55 percent of participants had heard about CRC screening, only 30 percent had ever had a screen themselves. Among elder tribal members queried during focus groups, nearly half had never had a colorectal screen, Sanderson says.

According to Sanderson, ongoing research is beginning to uncover a solid baseline for cancer knowledge among the Navajo Nation. "With this information, we can build a CRC screening campaign based upon cultural needs of this distinct population," Sanderson said. "It can also be a foundation for further research into cancer health disparities on the Navajo Reservation."

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; healthcare professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
(267) 646-0554
greg.lester@aacr.org
In Atlanta (November 27-30):
(404) 586-6124

New Perspectives on Health Disparities in Breast Cancer Research

registration@aacr.org () — Thu, 29 Nov 2007 12:00:00 GMT

ATLANTA - Breast cancer is a disease with a number of known genetic and behavioral risk factors, but scientists have seen that these risks are often compounded by social and racial inequalities. The question remains: how, exactly, do social disadvantages, genetics, race and culture add to the disparities faced by so many groups of women?

An Asian patient's attitude that the breast doesn't need to be preserved - primarily because of the culture's reduced emphasis on the breast and breast appearance - is an important consideration that leads many Asian women to choose a mastectomy, said a majority of physicians who participated in the investigators' survey.

Other reasons cited by physicians are that Asian women may choose a mastectomy because breast size in this population is smaller to begin with, so there is less breast to preserve, as well as factors such as age and unwillingness to travel for chemotherapy and radiation treatments which often are necessary following a lumpectomy.

Reasons for why Asian women choose mastectomy are important, say the NCCC team, because in order for a breast cancer patient to make the best clinical decision, she must be thoroughly educated on the benefits of each procedure. "For patients with early stage breast cancer where there are no clear clinical contraindications to breast-conserving treatment, a lumpectomy is less invasive than a mastectomy and it offers the same survival and potentially improved quality of life," said Jane T. Pham, an epidemiologist at NCCC and doctoral candidate in epidemiology at University of California, Davis.

In earlier research, the investigators found that a statistically significant greater number of Asian women (67.5 percent) choose to have a mastectomy over lumpectomy compared to Caucasian women (57.3 percent). And while the use of mastectomy has fallen among most populations over the past decade, it has not fallen as fast among Asian women, Pham says.

Under the direction of lead investigator Scarlett Lin Gomez, Ph.D., research scientist at NCCC and associate director of the Greater Bay Area Cancer Registry, Pham and her colleagues surveyed 80 physicians in the region who treat Chinese, Vietnamese and Filipina breast cancer patients. The survey asked physicians why they felt Asian women were choosing mastectomy significantly more often than other women.

While 74 percent of physicians surveyed said that consideration of cosmetic result is usually important to women treated with lumpectomy, most of the physicians felt cultural factors, such as a reduced emphasis on breast preservation, are the primary reasons for the higher rate of mastectomies among Asian women. Physicians also listed fear, both of reoccurrence and of radiation and chemotherapy, as another contributing factor.

All of these findings need to be probed further with Asian patients themselves, and this study is currently ongoing, Pham says. Funding for these continuing studies was provided by grants through the California Department of Health Services, National Cancer Institute and Centers for Disease Control and Prevention.

"Is it really a reduced significance of the breast when making treatment decisions, or is it fear about adverse outcomes?" Pham asked. "Although many of these cultural factors require additional research, awareness of these factors can allow physicians to directly address Asian patient concerns that may be influenced by culture, and fully inform the patient of their treatment options."

Obesity and risk for relapse of breast cancer in women of low socioeconomic status, Abstract no. A-34:

In one of the largest racially diverse studies of low income women, researchers found that women who are overweight or obese at the time they are diagnosed with breast cancer are at an increased risk of relapse.

Investigators from the Feist-Weiller Cancer Center at Louisiana State Health Science Center found that for each point gain of body mass index (BMI), the risk of cancer recurrence increased by four percent. For example, a breast cancer patient with a BMI of 30 had a 20 percent greater risk of relapse than a patient with a BMI below 25. (A BMI of 25-30 is considered overweight, and a BMI of 30 or greater is classified as obese.)

Not only was this risk evident in postmenopausal women, the researchers say, but the risk was present in premenopausal women, too. "We find that obesity, which is associated with poverty, is a significant factor in whether cancer recurs," said Amanda Sun, M.D., Ph.D., the study's lead investigator and oncologist at the Feist-Weiller Cancer Center. "The good news is weight is potentially a controllable risk factor."

The research team examined medical records for 349 women diagnosed with breast cancer from 1990 to 2004. Forty-five percent of participants were African-American, and the rest were Caucasian, making the study one of the largest with a high proportion of African-American breast cancer patients, Sun says. In this group, 25 percent lived in counties with high poverty rates; 20 percent of the patients received free health care; and 25 percent were enrolled in Medicaid.

"Poverty is an important marker for limited access to healthcare, late stage disease, and worse outcomes, and the fact is that poor adults are more likely to be obese," said Dolly Quispe, M.D., hematology-oncology fellow at the Feist-Weiller Cancer Center "The goal here is to determine if there is a correlation of obesity and poverty with breast cancer recurrence, and to quantify it."

African-American patients in this study were 62 percent more likely to have limited economic means, 88 percent more likely to be overweight and obese, and 46 percent more likely to be pre-menopausal, the researchers found.

Breast cancer recurred in 69 patients, and after investigators adjusted for body weight, race, menopausal status, age at diagnosis and cancer stage, BMI at diagnosis remained a statistically significant predictor of cancer recurrence. According to Quispe, low social economic status was a marginally significant predictor of relapse after adjusting for other factors. "We can see the relationship between poverty, obesity, and cancer recurrence in this study," Quispe said.

Also of note is the finding of a high rate of cancer relapse in younger patients, says Sun, "Many studies have found that obesity in postmenopausal women is a risk factor for breast cancer development, but those few that correlate excess body weight and cancer in premenopausal women have been mixed," Sun said.

The researchers say this kind of study was possible at the Feist-Weiller Cancer Center because that health center provides medical care to a significant portion of poor patients in Louisiana, a state with a poverty rate of 20 percent.

"This is a snapshot of breast cancer incidence in people without insurance," Quispe said. "It tells us that interventions targeting weight control could potentially improve outcomes in breast cancer."

The study was funded by the Feist-Weiller Cancer Center at LSU Health Sciences Center.

Disparities in receipt of lymph node assessment among early stage female breast cancer patients, Abstract no. A-65:

Examining nearby lymph nodes while a woman is undergoing surgery for early stage breast cancer is a recommended practice to determine whether the cancer has spread, although there are valid clinical reasons to omit this procedure. However, researchers at the American Cancer Society (ACS) have found that 11 percent of almost 200,000 patients in a national sample of individuals with cancer did not undergo the procedure, and these women were significantly more likely to be elderly or African-American, have no health insurance or live in an area whose residents have a low level of education.

The findings are concerning because they suggest clinical factors may not be the primary basis for decisions on breast cancer care for some disadvantaged patients, as they should be, researchers say.

"We found that significant disparities exist in who received axillary lymph node assessment, and without this procedure, an oncologist cannot appropriately stage a woman's cancer and determine optimal therapy," said Michael Halpern, M.D., Ph.D., strategic director of Health Services Research for the ACS.

Investigators specifically found that women without insurance were 24 percent less likely to receive the lymph node assessment compared to those with private insurance. Women who lived in areas with low levels of education were 13 percent less likely than those from high education areas, and African-American patients were 10 percent less likely to have the procedure than white patients.

They also found that age was a "huge" factor in who received a lymph node assessment: women age 73 or older were three times less likely to receive the procedure than were patients age 51 or younger, researchers said.

Standard practice guidelines for axillary node dissection during lumpectomy or mastectomy surgery specify when this procedure can be considered optional, such as for elderly patients, patients with other serious illnesses, or patients for whom lymph node results wouldn't affect choice of therapy.

"Ideally, factors such as race and insurance status shouldn't play any role in who receives this procedure, yet that is what we found. And while age is an important factor in deciding whether or not to perform lymph node assessments, we certainly didn't expect a three-fold difference," Halpern said.

Other studies have indicated that disparities in care may result from three different sources: structural barriers (such as health insurance or type of hospital), physician/clinical factors, and patient factors. "All three of these may be important in the disparities we observed for axillary node dissection," Halpern said.

"These disparities could result from differences in sites of care or practice patterns among healthcare providers that predominantly treat poor or uninsured women, or could reflect appropriate application of clinical guidelines in some cases," Halpern said. "We can't be sure why these disparities occur, because we just don't know how those decisions are being made at the patient and physician levels."

To conduct the study, researchers examined data from 196,732 patients who had surgery to treat early stage breast cancer from 2003-2005 from the National Cancer Database, a hospital-based registry sponsored by the ACS and the American College of Surgeons. All of these hospitals had cancer programs accredited by the Commission on Cancer; approximately 70 percent of cancer patients nationwide are treated at these hospitals.

"We need to find out why these disparities exist and what to do to make sure that everyone is getting excellent cancer care," Halpern said.

Gene expression analysis of African-American and European-American breast tumors, Abstract no. B-93:

While observed differences in breast cancer survival between African-American and Caucasian women are often attributed to disparities in socio-demographic and access to healthcare factors, recent studies have shown that, even when accounting for these factors, African-American women still fare worse than Caucasian women. In a study of how genes are activated in breast cancer tumors, researchers at the National Cancer Institute (NCI) have demonstrated that there are discernable racial and ethnic differences in the biology of these tumors.

In particular, their findings revealed that many genes related to tumor immunobiology, inflammation, and angiogenesis are expressed differently in tumors from African-American women than in those from Caucasian women. The data could indicate that inflammation and other immune system processes play a stronger role in the development and progression of cancer in African-American women, says Damali Martin, Ph.D., postdoctoral fellow at NCI's Center for Cancer Research.

According to Martin, African-American breast cancer patients on the whole tend to have a greater prevalence of a more aggressive form of breast cancer, one that is less likely to respond to hormone therapy and more likely to spread to lymph nodes.

Martin and her colleagues examined gene expression profiles - an indicator of which genes are active -- in microdissected breast tumors from 35 patients with invasive breast cancer, including 18 African Americans and 17 Caucasians.

The researchers identified racial discrepancies in the gene profiles that point to significant differences in several biological pathways, including how tumor cells interact with the immune system and the mechanisms for angiogenesis - the development of blood vessels that feed tumors. The researchers point out that many of these genes are also active in inflammatory diseases. Previous research has shown a link between inflammatory diseases, such as chronic cholitis, and cancer, Martin says.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
(267) 646-0554
greg.lester@aacr.org
In Atlanta (November 27-30):
(404) 586-6124

Genetic Differences Point to Ethnic and Racial Disparities in Colorectal Cancer Risk

registration@aacr.org () — Wed, 28 Nov 2007 12:00:00 GMT

ATLANTA - Risk of developing colorectal cancer is known to differ across ethnic and racial groups, and now an analysis of 26 studies, involving over 25,000 participants shows that some of these disparities might be explained by distinct patterns of genetic inheritance. A team of researchers, led by investigators at the University of Pittsburgh, present their findings today in Atlanta at the American Association for Cancer Research conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, being held November 27-30.

The researchers found that people who have two "T" copies of the gene that metabolizes folate, a chemical needed to produce and maintain new cells, are 19 percent less likely to develop colorectal cancer than are individuals with two "C" copies of the gene.

By using individual data collected through the Genetic Susceptibility to Environmental Carcinogens study, a collaborative pooled analysis based at the University of Pittsburgh Medical Center and begun in 1997, they were able to look at genetic inheritance in different racial and ethnic groups. The investigators found that the odds of individuals developing colorectal cancer with two "T" genes versus two "C" genes was 31 percent less in Asians, 8 percent less in Caucasians, and 4 percent more in African-Americans, although results were only statistically significant in the Asian population. Conversely, Latinos who inherited one copy of each gene instead of two "C" genes had a 20 percent higher risk of developing the cancer. However, this result was not statistically significant.

"This analysis shows that homozygosity for the T copy of this gene may be protective in different degrees against colorectal cancer in some populations but not in others," said lead investigator, Mary A. Garza, Ph.D., M.P.H., deputy director of the Center for Minority Health in the University of Pittsburgh's Graduate School of Public Health.

Garza says this is the first pooled analysis to explore the association between specific genes and the risk of developing colorectal cancer across racial/ethnic populations. "We are trying to unlock the role genetics, through gene-environment interactions, may play in understanding the underlying causes of health disparities," Garza said.

Even though deaths rates from colorectal cancer have been declining in the United States, African-Americans and other minority populations experience a disproportionate share of this cancer burden, Garza says. "This disparity exists even after accounting for various environmental and social factors, so it makes sense that genetics could play a contributing role in this cancer disparity," she said.

The researchers focused on the metabolic enzyme 5 10-methelenetetrahydrofolate reductase (MTHFR), whose role is to maintain folate in the blood in order to prevent the buildup of homocysteine, a chemical byproduct that is toxic to cells. The CC version of MTHFR is considered the wild type - the version most common in the population as a whole - and the CT or TT alleles carry a variant "T," a point mutation in which a thymine nucleic acid is substituted for a cytosine in the gene's DNA. Compared to CC, enzymatic activity of the CT mutation is reduced to 65 percent; TT has 30 percent the enzymatic activity of CC.

One common variation of the gene, called C677T, has been associated with a lower risk of colorectal cancer in individuals with high levels of folate and low levels of alcohol use, Garza says.

Their finding that the TT version of the gene seems to offer protection against colorectal cancer in Asian, and possibly in other groups except Latinos warrants further examination, Garza says. "Normally, if one carries the recessive TT which means reduced enzyme activity, you would expect a higher risk of developing colorectal cancer; however, the opposite is true," she said.

"One could speculate that C677T may contribute in combination with environmental exposures to the differences in colorectal cancer prevalence in racial or ethnic populations," Garza said. "These findings warrant larger studies to evaluate gene-environment interactions for the MTHFR polymorphism and colorectal cancer risk in different racial or ethnic populations."

Funding for this study was provided by grants from the Multidisciplinary Clinical Research Scholars Program and the National Center on Minority Health & Health Disparities of the National Institutes of Health.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
(267) 646-0554
greg.lester@aacr.org
In Atlanta (November 27-30):
(404) 586-6124

Cancer Risks for Urban African-American Women Grow as Healthy Diets Become More Difficult to Maintain, Study Shows

registration@aacr.org () — Wed, 28 Nov 2007 12:00:00 GMT

ATLANTA - Women living in the inner city have difficulty meeting dietary goals that could help prevent cancer, according to a report from Johns Hopkins University researchers. In a study of African-American women living in public housing within Washington, D.C., the researchers found that the majority met one - or none - of five dietary goals suggested to reduce the risk of developing cancer. In particular, these women were unlikely to eat a healthy diet that included the recommended amount of fresh fruits and vegetables.

Their analysis also linked high risk dietary behaviors with younger age, depression, smoking and being born within the District of Columbia. The researchers present their findings today in Atlanta at the American Association for Cancer Research conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, being held November 27-30.

"African-American women, in general, face a worse cancer incidence and mortality rate than most other ethnic groups, and poor African-American women are at an even greater disadvantage," said Ann C. Klassen, Ph.D., associate professor in the Department of Health, Behavior, and Society at Johns Hopkins University's Bloomberg School of Public Health. "Improving diet is one effective way to help these women lower their risk for developing cancer."

Since diet and behavior are intertwined, Klassen says, the researchers needed to get a better understanding of the lifestyle of African-American women in the District of Columbia's low resource neighborhoods in order to assess the needs of the community.

Klassen and her colleagues analyzed data from 156 African-American female residents of 11 public housing communities across Washington. The women participants gave information regarding what they ate and drank - as well as other behaviors - over several 24 hour periods, providing 468 such diet-related recalls to researchers.

In particular, the researchers examined the diet recalls to see if the researchers met the ideal goals of five characteristics of a cancer-preventing diet: adequate consumption of fruits and vegetables; low percentage of fat intake; moderate caloric intake, no alcohol consumption; and adherence to the USDA's "Healthy Eating Index," a measure of the overall quality of diet. They also looked at when and where these women ate, as well as with whom they were eating. "We were looking to take a holistic approach to the women's diet, one that not only looks at food consumed, but also their general behavior and circumstances, which can impact how they make dietary choices," Klassen said.

The majority of women, about 61 percent, failed to meet the goals for more than one of these characteristics, with many meeting none. Less than one percent met all the ideal standards in each of the five categories. Only 15 percent of women reported eating at least five servings of fruits or vegetables, Klassen says, however 64 percent reported no alcohol consumption during the recall days.

"Many women drank soda, and ate convenience and prepared foods, even when they sat down with their families for a meal," Klassen said. "Younger adults, especially, seem to lack the skills to build a well-balanced diet - skills that our survey shows that older generations of women still possess."

Where they lived among the public housing communities also made a difference in whether the women reported eating a cancer-preventing diet. "We see that women who can take advantage of community vegetable gardens - which are often missing in inner-city neighborhoods - are more likely to eat a healthier diet than women who do not have those amenities in their neighborhoods," Klassen said.

Klassen and her colleagues also demonstrated a positive relationship between the average education level in neighborhoods, namely the proportion of residents holding high school diplomas, and dietary behaviors in African-American women.

However, their analysis also uncovered traits that negatively affected cancer risk, including smoking, depressive symptoms and youth. They also found that women who were born in Washington, D.C., reported far worse dietary behaviors than women who had moved to the city from elsewhere. "Overall, we are getting a clear depiction of the role of diet as a connection between social status and health," Klassen said. "Women in poverty, in particular, suffer from the lack of good dietary information as well as a variety of healthy foods, which can compound other problems in their lives."

With this information, Klassen says it will be easier to craft new educational interventions to help African-American women and their families lower the cancer risk and improve their overall health.

This study was funded by the American Cancer Society and the Maryland Cigarette Restitution Fund. Researchers in this study include Katherine Smith, Ph.D., and Laura Caulfield, Ph.D., of Johns Hopkins Bloomberg School of Public Health, and Maureen Black, Ph.D., from the University of Maryland School of Medicine.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
(267) 646-0554
greg.lester@aacr.org
In Atlanta (November 27-30):
(404) 586-6124

Bernstein Honored with AACR-Prevent Cancer Foundation Award for Excellence in Cancer Prevention Research

registration@aacr.org () — Wed, 28 Nov 2007 12:00:00 GMT

PHILADELPHIA - Leslie Bernstein, Ph.D., a research expert on the effects of hormones and physical activity on cancer risk, late effects of cancer treatment, the impact of lifestyle on cancer prognosis, and quality of life after cancer, has been selected to receive the sixth annual American Association for Cancer Research (AACR)-Prevent Cancer Foundation Award for Excellence in Cancer Prevention Research.

The award is given annually to a scientist for seminal contributions to the field of cancer prevention research in basic, translational, clinical, epidemiological, or behavioral science.

Bernstein, professor and director of the Department of Cancer Etiology and dean for Faculty Development at City of Hope in Duarte, Calif., is being honored for her distinguished research career in cancer epidemiology and prevention, spanning nearly 25 years of discovery. She is internationally recognized as a preeminent researcher and scholar whose work has vast implications on the quality of life of cancer survivors.

Bernstein's early work examined the effects of exercise and body weight on the onset of puberty and hormonal patterns during adolescence. This research challenged the paradigm that epidemiologic risk factors for breast cancer were largely unmodifiable; demonstrated that physical activity can directly decrease breast cancer risk; and laid the foundation for subsequent epidemiologic studies and clinical trials focused on understanding the joint contributions of physical activity, weight and associated biologic mechanisms to the etiology of breast cancer. This area is now a primary international focus of cancer prevention and control research.

In later research, Bernstein identified ethnicity-related variations and determinants of poor prognosis in breast cancer patients. Bernstein is also a pioneer in the development and use of epidemiologic methods for evaluating the long-term side effects of cancer treatment in cancer survivors. Using a multicenter population-based setting she substantiated the association between tamoxifen use and risk of subsequent endometrial cancer in women and demonstrated for the first time that this association is potentially restricted to women who had previously used unopposed estrogen therapy or who were obese at the time of their breast cancer diagnosis. Recently, in a large HMO-based study of risk of stroke in relation to breast cancer therapies, she demonstrated the absence of an association between tamoxifen and stroke risk but an increased stroke risk following chemotherapy.

Past winners of AACR-Prevent Cancer Foundation Award for Excellence in Cancer Prevention include Stephen Hecht, Ph.D., of The Cancer Center at the University of Minnesota, in 2006; Scott M. Lippman, M.D., of The University of Texas M. D. Anderson Cancer Center, in 2005; David S. Alberts, M.D., of the Arizona Cancer Center, in 2004; Waun Ki Hong, M.D., also of the M. D. Anderson Cancer Center, in 2003; and Michael B. Sporn, M.D., of the Dartmouth Medical School, in 2002.

Bernstein received her B.A. in Mathematics, M.S. in Gerontology, and Ph.D. in Biometry from the University of Southern California. She rose through the academic ranks of USC, culminating with her current positions of Professor of Preventive Medicine and the first AFLAC, Incorporated Chair in Cancer Research. Bernstein was named Professor Emeritus of USC following her retirement there in 2007.

Bernstein has received numerous honors and awards for her scientific accomplishments, including the American Society for Preventive Oncology Distinguished Achievement Award, the USC Presidential Medallion (the University's highest honor), and the Keck School of Medicine Stevely Hoffman Achievement Award. Her distinguished lectureships include the Cutter Lectureship at Harvard University, the Meadow Brook Lecture at Wayne State and Oakland Universities, and the Sloan Memorial Lecture at Boston University. Bernstein has authored or co-authored more than 400 scientific papers and publications.

An active member of AACR since 1995, Bernstein has served in various capacities, including as an Editorial Board member of Cancer Epidemiology, Biomarkers and Prevention, as a participant in Women in Cancer Research activities, and as a member of several committees.

Bernstein will give an award lecture entitled, "Breast Cancer Prevention: Learning from the Past, Mentoring the Future," on Thursday, December 6, 2007, at the Sixth Annual AACR International Conference on Frontiers in Cancer Prevention Research. This foremost meeting on cancer prevention research will be held December 5-8, 2007 at the Philadelphia Marriott Downtown in Philadelphia.

The AACR is pleased to co-sponsor this award with the Prevent Cancer Foundation. The Foundation is a national, non-profit health foundation with a single mission: the prevention and early detection of cancer through scientific research and education.

Editor's Note: For a high resolution photo of Dr. Bernstein, please e-mail Angela Showell at angela.showell@aacr.org.

# # #

Contact:
Jennifer Ryan
(267) 646-0558
jennifer.ryan@aacr.org

The Latest on Cancer Prevention through Diet, Obesity, Therapeutics and Public Health Policy Research Showcased

registration@aacr.org () — Wed, 28 Nov 2007 12:00:00 GMT

Sixth Annual AACR Conference on "Frontiers in Cancer Prevention Research" Philadelphia, December 5-8, 2007

PHILADELPHIA - Perhaps the best way to fight cancer is to prevent it from developing in the first place. The latest biological, medical and social research behind cancer prevention will be the focus of the American Association for Cancer Research's Sixth Annual International Conference on Frontiers in Cancer Prevention Research, to be held December 5 to 8 at the Philadelphia Marriott Downtown in Philadelphia, Pennsylvania.

"This meeting has become a major venue for presenting cutting-edge research in basic, clinical, epidemiologic, and behavioral science," said meeting chair Andrew J. Dannenberg, M.D., professor of medicine at the Weill Medical College of Cornell University. "As the only comprehensive conference on cancer prevention in the world, it continues to foster important transdisciplinary interactions that are vital to making critical discoveries."

The conference will cover a wide variety of cancer prevention topics, including some of the latest developments in clinical genetics, infectious diseases, imaging, and metabolism. Two special "Controversy Sessions" will focus on the scientific debates regarding current practices in breast cancer prevention and the potential role of smokeless tobacco in the fight against smoking-related cancers.

The Philadelphia conference brings together scientists and other professionals, working in a variety of disciplines, to discuss the latest findings in the field and to stimulate the development of new research in cancer prevention. The conference was also designed to promote public, academic, government, and industry awareness of the vital importance of cancer prevention science in reducing cancer incidence and mortality.

Highlights of this conference will include breaking news:

Raw, but not cooked, cruciferous vegetables, such as broccoli or cauliflower, can lower one's risk of developing bladder cancer, scientists at the Roswell Park Cancer Institute report.

Gaining weight following breast cancer diagnosis greatly reduces a woman's chances of surviving the disease, according to epidemiologists at Johns Hopkins University.

Eating black raspberries could slow the growth of precancerous lesions that lead to esophageal adenocarcinoma, says researchers at Ohio State University.

The HPV vaccine has been shown to prevent cervical cancer, but are all Americans aware that the vaccines are safe, effective and, above all, available? Researchers at Columbia University report that many urban physicians working in under-resourced communities are struggling to get patients vaccinated.

A commercially available fruit drink might lower one's risk of developing prostate cancer, say researchers at the University of Sydney. Their findings in animal models of prostate cancer show the beverage, a cocktail of numerous known anti-cancer plant products, shows promise for human trials.

Diet and exercise have a demonstrable effect on lung cancer risk, say researchers at the University of Texas M. D. Anderson Cancer Center. Theirs is the first lung cancer risk prediction model that examines both diet and physical activity - among smokers, non-smokers and former smokers - using the USDA pyramid serving guidelines.

Capping off AACR's scientific meeting is a free, public education program entitled "Cancer Answers: A Public Forum on Cancer Prevention." Scientists and cancer advocates will help educate the Philadelphia community on cancer prevention through an interactive dialogue, sharing their research and answering questions about diet, lifestyle, exercise, chemoprevention, clinical trials, genetics, personalized medicine, survivorship and cancer education. Information on resources for cancer patients and their families, as well as general information on cancer will also be available from local advocacy and community education groups.

Susan G. Komen for the Cure is recognized as the lead supporter of "Frontiers in Cancer Prevention Research" with additional support from the American Cancer Society, National Cancer Institute, and Centers for Disease Control and Prevention.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In the press room (December 5-8):
215-409-4766

Emerging Research Highlights How Race, Ethnicity and Socio-economic Factors Affect Cancer Outcomes

registration@aacr.org () — Tue, 20 Nov 2007 12:00:00 GMT

American Association for Cancer Research hosts "The Science of Cancer Health Disparities" Atlanta, November 27-30, 2007

PHILADELPHIA - The latest biological, clinical and social research behind how cancer affects different racial and ethnic groups will be the focus of the first American Association for Cancer Research conference on the topic, entitled "The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved." The meeting is to be held November 27 to 30 at the Atlanta Marriott Marquis in Atlanta, Georgia.

"Racial and ethnic disparities in cancer incidence and mortality are well documented," said meeting co-chair Olufunmilayo I. Olopade, M.D., professor of medicine and human genetics at the University of Chicago and director of the University of Chicago Medical Center's Cancer Risk Clinic. "While data suggest that access to quality care is a factor in cancer disparities, other factors also play a major role, including tumor biology, genetics, lifestyle and behavior, screening policies, comorbidities, environmental exposure and risk, quality of and response to therapy, and post-therapeutic surveillance."

Research presented at the conference will include the science behind how cancer affects populations of different ethnicities, as well as the function and structure of community-based research and cancer awareness programs designed to reach disadvantaged populations.

The conference traces its genesis to a think tank session on research issues related to cancer health disparities in October 2006, sponsored by AACR and the National Cancer Institute Center to Reduce Cancer Health Disparities. The think tank brought together clinical researchers, epidemiologists, molecular biologists, social scientists, geneticists, pathologists, and patient advocates, to discuss the emerging data and advance this new and growing field of research.

"It was evident from the proceedings of the think tank that there were many scientific challenges to address and overcome and that the next step to moving the field forward would be to hold a multidisciplinary conference on the science of cancer health disparities," said meeting co-chair Timothy Rebbeck, Ph.D., Professor of Epidemiology at the University of Pennsylvania's School of Medicine.

The Atlanta conference brings together scientists and other professionals, working in a variety of disciplines, to discuss the latest findings in the field and to stimulate the development of new research in cancer health disparities. Carcinogenesis, biomarkers, epidemiology, prevention, cancer communications, translational research, treatment, health economics and survivorship issues will be highlighted. The meeting is co-sponsored by the NCI Center to Reduce Health Disparities and the Minorities in Cancer Research council of the AACR.

"This conference is the first of its kind in that it will address various topics in basic science, clinical research, population science, behavioral research, and cancer survivorship," said meeting co-chair John D. Carpten, Ph.D., senior investigator and director in the Integrated Cancer Genomics Division at the Translational Genomics Research Institute. "The meeting will provide a powerful forum to identify risk factors and barriers to the reduction and elimination of cancer health disparities."

Olopade, Rebbeck and Carpten will host a press briefing to give reporters background on the emerging field of cancer health disparities and an update on the state of the science. Additional highlights of this conference will include breaking news on:

Ethnic disparities in colorectal cancer death rates have an underlying genetic basis, according to an analysis of 26 studies, involving over 25,000 participants, by researchers from the University of Pittsburgh.

Differences in lymph node assessment among breast cancer patients who undergo surgery. The practice, which helps to determine whether the cancer has spread and thus informs treatment decisions, is optional, yet certain groups of women are less likely to undergo the procedure, according to researchers at the American Cancer Society.

Assessing the cancer care needs of recent Hispanic immigrants in Nashville, Tennessee, has become a priority for a coalition of local universities and community groups. Like many communities across America, Nashville has faced a massive wave of immigrants in the last decade, yet not much is known about the healthcare needs of this largely uninsured population, despite their expressed interest in receiving cancer information and participating in clinical trials, researchers at Tennessee State University report.

Aggressive prostate cancer in African-American men might be exacerbated by the effects of obesity and diabetes on PSA levels, a common prostate cancer screening technique, report researchers from Vanderbilt University.

Cultural views among Asian ethnic groups might influence treatment recommendations for Asian breast cancer patients, according to researchers from the Northern California Cancer Center.

Capping off AACR's scientific meeting is a free, public education program entitled "Cancer Answers: A Public Forum on Cancer Health Disparities." Scientists and cancer advocates will help educate the Atlanta community on cancer health disparities through an interactive dialogue, sharing their research and answering questions about race and cancer, clinical trials, genetics, personalized medicine, survivorship and cancer education. Information on resources for cancer patients and their families, as well as general information on cancer and health disparities will also be available from local advocacy and community education groups.

Susan G. Komen for the Cure is recognized as the lead supporter of "The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved" with additional support from Eli Lilly and Amgen.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
(267) 646-0554
greg.lester@aacr.org
In Atlanta (November 27-30):
(404) 586-6124

Researchers Chart the Genetic Mechanisms behind the Genesis of Fat Cells

registration@aacr.org () — Tue, 06 Nov 2007 12:00:00 GMT

Findings from the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment, Singapore, November 4-8, 2007

SINGAPORE -- Obesity is a well known risk factor for prostate, breast and colon cancer, but recent studies have shown that a protein responsible for generating fat cells also plays an important role in cancer. Researchers at the Genome Institute of Singapore have conducted, for the first time, a genome-wide analysis of how the protein, called perixosome proliferator-activated receptor gamma (PPARg), turns on various genes related to obesity.

Simply suppressing the protein entirely could prevent the generation of adipocytes - the precursors to fat cells - the researchers say, but it would decrease the protein's beneficial properties. Instead, the researchers believe that by identifying the gene targets of PPARg, they could open up new targets for drug development against a number of diseases, including obesity, diabetes and cancer. They present their findings today at the AACR Centennial Conference on Translational Cancer Medicine.

"To date, only a limited number of direct targets for PPARg have been identified. Our findings provide a genome-wide map of PPARg binding sites during the course of adipocyte differentiation," said M. Sabry Hamza, Ph.D., a postdoctoral research fellow at the Genome Institute of Singapore, a division of Singapore's Agency for Science, Technology and Research (A*STAR). "These results together with the expression profile of genes that are dependent of PPARg expression provide us with clues into the transcriptional circuitry during adipogenesis, the process by which adipocytes differentiate into different types of fat tissue."

With funding from A*STAR, "we have identified direct targets of PPARg, that when inhibited lead to a dramatic reduction of adipogenic potential," Hamza said. "Ongoing analysis will help us decipher whether these direct targets control adipogenesis, insulin sensitization or determination of fat cell type."

According to Hamza, PPARg inhibits the proliferation and lowers the threshold for apoptosis -- the process by which cancer cells destroy themselves. "In addition, significant increase in tumor suppressor BRCA1 is induced when breast cancer cells are exposed to PPARg agonists," said Hamza. "Although indirect, the role of PPARg as it relates to obesity and cancer is intriguing."

So far, Hamza and his colleagues have identified a number of new PPARg target genes which are connected to adipogenesis and insulin sensitivity. Currently available marketed oral hypoglycemic drugs, although very potent in treating type II diabetes, cause detrimental sides effects including weight gain, liver toxicity and heart disease, says Hamza. "Using drugs which target specifically those PPARg targets regulating insulin sensitivity could hence present a safer and more efficient therapeutical approach," said Hamza.

According to Hamza, the researchers' next step will be to apply their data to mouse models in order to compare PPARg activity in fat tissue of mice under high-fat and normal conditions and to further characterize the regulation of PPARg target genes identified in this study.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 14 research institutes and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The Agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.

The Genome Institute of Singapore (GIS) is a member of the Agency for Science, Technology and Research (A*STAR). It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

Contact:
Genome Institute of Singapore
Winnie Serah Lim
(65)9730 7884
limcp2@gis.a-star.edu.sg

American Association for Cancer Research
Staci Vernick Goldberg
(267) 646-0616
Staci.Goldberg@aacr.org

Drug Slows Prostate Tumor Growth by Keeping Vitamin A Active

registration@aacr.org () — Tue, 06 Nov 2007 12:00:00 GMT

Findings from the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment, Singapore, November 4-8, 2007

SINGAPORE -- A novel compound that blocks the breakdown of retinoic acid, derived from vitamin A, is a surprisingly effective and "promiscuous" agent in treating animal models of human prostate cancer, say investigators from the University of Maryland, Baltimore (UMB).

Daily injections of the agent VN/14-1 resulted in up to a 50 percent decrease in tumor volume in mice implanted with human prostate cancer cells, reported Aakanksha Khandelwal, Ph.D., today at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine. No further tumor growth was seen during the five-week study, Khandelwal reports.

Importantly, VN/14-1 exerted its effects in multiple ways, which is the hallmark of a so-called promiscuous drug, according to the study's senior investigator, Vincent C.O. Njar, Ph.D., associate professor in the Department of Pharmacology and Experimental Therapeutics within UMB's School of Medicine.

"This potent agent causes cancer cells to differentiate, forcing them to turn back to a non-cancerous state - which is what we expected it would do - but it also stops cancer growth by arresting the cell cycle and pushes cells to die by inducing programmed cell death," Njar said.

"These functions were unexpected and wonderfully surprising," he said. "I am not aware that any other drug currently used to treat prostate cancer targets so many pathways."

Vitamin A, when converted by the body into retinoic acid, is known to be involved in maintaining the normal growth of cells, and other research has shown that prostate cancer cells contain five to eight times less retinoic acid than normal prostate cells. Njar's laboratory developed a number of compounds, including VN/14-1, with the aim of inhibiting the normal breakdown of retinoic acid in cancer cells.

The agent is similar in function to the well-known acne and anti-aging therapy, Retin-A, as well as to the leukemia drug Vesanoid. These products, known as retinoids, add all-trans retinoic acid (ATRA) to skin or cancer cells. VN/14-1, which is a retinoic acid metabolism blocking agent (RAMBA), works by inhibiting the breakdown of ATRA, keeping more retinoic acid available within cancer cells so that the chemical can redirect these cells back into their normal growth patterns, which includes programmed cell death.

"Our idea is that rather than give extra ATRA, we would prevent ATRA already available within cells from being broken down," Njar said. "We now call VN/14-1 an atypical RAMBA because in addition to blocking ATRA metabolism, it has other multiple desirable anti-cancer effects."

VN/14-1 works by blocking the CYP26 enzyme that actually transforms ATRA into inactive compounds, he says. The researchers have successfully tested VN/14-1 in breast cancer cells and have been funded to study the compound in preclinical studies that can lead to a Phase I human clinical trial.

In this study, the researchers found in mouse models of human prostate cancer that a 5 mg/kg (milligram per kilogram) dose injected daily resulted in a 33 percent reduction in tumor size; a dose twice as large reduced tumors by 50 percent.

They also tested a dose of 20 mg/kg through oral and intravenous administration to study the concentration of VN/14-1 in the blood over time in rats. They found that the amount of VN/14-1 in the blood after oral administration was exceptionally high compared to intravenous VN/14-1. This indicates that VN/14-1 should be tested orally as this is the preferred route of drug administration in humans, Njar says. "Giving an agent orally in small doses is exactly what you want in an anti-cancer drug," he said.

The study was funded by grants from the National Institutes of Health and National Cancer Institute, the U.S. Department of Defense, and UMB's Marlene and Stewart Greenebaum Cancer Center.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Genome Institute of Singapore
Winnie Serah Lim
(65)9730 7884
limcp2@gis.a-star.edu.sg

American Association for Cancer Research
Staci Vernick Goldberg
(267) 646-0616
Staci.Goldberg@aacr.org

Antioxidants Could Provide All-Purpose Radiation Protection

registration@aacr.org () — Sun, 04 Nov 2007 12:00:00 GMT

Findings from the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment, Singapore, November 4-8, 2007

SINGAPORE -- Two common dietary molecules found in legumes and bran could protect DNA from the harmful effects of radiation, researchers from the University of Maryland report. Inositol and inositol hexaphosphate (IP6) protected both human skin cells and a skin cancer-prone mouse from exposure to ultraviolet B (UVB) radiation, the damaging radiation found in sunlight, the team reported today at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine.

According to the researchers, inositol and IP6 could decrease the severity of side effects from radiation therapy, saving healthy cells while simultaneously increasing the potency of the treatment against cancer cells. Both molecules are potent antioxidants, the Maryland researchers say, capable of preventing reactive molecules from injuring DNA and turning cells cancerous.

"Both of these potent antioxidants have been shown to have broad-spectrum anti-tumor capabilities, and now our studies confirm the degree to which these molecules protect against the DNA-damaging effects of ionizing radiation," said Abulkalam M. Shamsuddin, M.D., professor of pathology at the University of Maryland School of Medicine. "Radiation damage is radiation damage, regardless of the source, so there could also be a protective role for IP6 in any form of radiation exposure, whether it is from a therapeutic dose or from solar, cosmic or nuclear sources."

While both inositol and IP6 are related to B vitamins, they are not considered essential dietary nutrients. In the 1980s, however, researchers discovered that these molecules, abundant within the hulls of seeds and grains, had definitive protective effects against colorectal cancer.

Inspired by reports of a clinical trial begun in 2001 at Clinical Hospital in Split, Croatia, which suggested IP6 enhanced the effectiveness of radiotherapy while lessening the side effects, Shamsuddin and his colleagues sought to investigate the extent of the protective properties of these molecules. With funding from IP-6 Research, Inc., a company formed by Shamsuddin, the researchers began a study to determine how human skin cells responded to UVB radiation when dosed with IP6.

Normally, cells permanently damaged by radiation undergo a genetically programmed process of cell suicide, called apoptosis. Shamsuddin reports that UVB-irradiated human keratinocytes, when treated with IP6, were more likely to survive. Untreated skin cells were more likely to undergo apoptosis, indicating that the DNA in those cells was damaged irreparably and fatally. According to Shamsuddin, the treated cells take an extended pause at the point in the cellular life cycle where innate mechanisms repair DNA before the cell divides.

"IP6 certainly has some interactivity with DNA, but how exactly it works to repair DNA is still something of a mystery. There are reports that IP6 binds with DNA repair molecule Ku to bring about the repair process," Shamsuddin said. "More importantly, we still don't know how IP6 can appear to help healthy cells live while also enhancing the ability of radiation to kill cancer cells."

Shamsuddin and his team found that when mice engineered to be prone to skin cancer were given drinking water containing a two-percent solution of IP6, they were much less likely to develop tumors. Twenty-three percent of treated mice developed tumors, compared to 51 percent of untreated, or control mice, which developed tumors. Moreover, the mice in the treated group that did develop cancer had only half as many tumors as the control mice.

Similarly, Shamsuddin saw that mice treated with a topical cream containing four percent IP6 plus one percent inositol were also less likely to develop tumors. When they administered the cream an hour before UVB irradiation akin to sun exposure, 62 percent of the treated mice developed tumors compared to 76 percent of the control mice. According to Shamsuddin, their findings indicate that either topical or ingested IP6 might confer protection against ionizing radiation.

Ionizing radiation occurs in the environment in many forms, originating from both natural and human-contrived sources. In humans, exposure to ionizing radiation occurs primarily through therapeutic techniques (such as anticancer radiotherapy), and sunbathing. Astronauts, pilots and passengers of high-altitude aircraft also are inordinately exposed to solar radiation. Such radiation exposures have a cumulative effect, increasing the chances of developing cancer over time, researchers say. "It is possible that people regularly exposed to ionizing radiation, such as airline pilots, frequent fliers or people who handle radioactive materials, might take IP6 prophylactically to prevent possible long term effects of exposure," Shamsuddin said.

According to Shamsuddin, IP6 could also offer protection against accidents or purposeful incidents involving nuclear material. "It could also be advisable to use IP6 plus inositol as a cautionary treatment following a nuclear disaster or dirty bomb," Shamsuddin said.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Genome Institute of Singapore
Winnie Serah Lim
(65)9730 7884
limcp2@gis.a-star.edu.sg

American Association for Cancer Research
Staci Vernick Goldberg
(267) 646-0616
Staci.Goldberg@aacr.org

Curry-derived Molecules Might be Too Spicy for Colorectal Cancers

registration@aacr.org () — Sun, 04 Nov 2007 12:00:00 GMT

Findings from the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment, Singapore, November 4-8, 2007

SINGAPORE -- Curcumin, the yellowish component of turmeric that gives curry its flavor, has long been noted for its potential anti-cancer properties. Researchers from Tohoku University in Sendai, Japan, report on an apparent improvement upon nature: two molecular analogues of curcumin that demonstrate even greater tumor suppressive properties. The team presented their findings from the first test of these molecules in a mouse model of colorectal cancer today at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine.

According to Tohoku University researcher Hiroyuki Shibata, M.D., curcumin is one of the most widely studied plant-based chemicals with anti-cancer properties. Research has associated curcumin with several distinct actions, including the suppression of genes that promote cell growth (for example, the destruction of the pro-cancerous protein β catenin), and induction of programmed cell death (apoptosis) in colorectal cancer.

Unfortunately, natural curcumin has what researchers term "low bioavailability" -- the molecule quickly loses its anti-cancer attributes when ingested, Shibata says. With the aim of improving the therapeutic potential of curcumin, Shibata and his colleagues synthesized and tested 90 variations of the molecule's structure. Two, GO-Y030 and GO-Y031, proved to be more potent and bioavailable, than natural curcumin.

"Our new analogues have enhanced growth suppressive abilities against colorectal cancer cell lines, up to 30 times greater than natural curcumin," said Shibata, associate professor in the Department of Clinical Oncology at the Institute of Development, Aging and Cancer at Tohoku University. "In a mouse model for colorectal cancer, mice fed with five milligrams of GO-Y030 or GO-Y031 fared 42 and 51 percent better, respectively, than did mice in the control group."

In 2006, the researchers published basic safety and structural data for GO-Y030 and GO-Y031 in Molecular Cancer Therapeutics, a publication of the American Association for Cancer Research, and they continue to study the mechanisms behind the molecules' apparent potencies. In its natural form, the curcumin molecule is composed of two ring structures linked by a chain of seven carbon atoms. The active ring structures of GO-Y030 and GO-Y031, however, are linked by a shorter, five-carbon chain, which Shibata says might - for reasons still under investigation -account for their enhanced potency.

Like curcumin, the researchers believe the new analogues have clinical potential that extends beyond colorectal cancer. "In addition to colorectal cancer, the β catenin-degrading abilities of these molecules could apply to other forms of cancer, such as gastric cancer," said Shibata. "Like curcumin, these analogues also down-regulate a number of gene products, such as NF-kappa B, ErbB2, K-ras, that are also implicated in breast, pancreas and lung cancers among other diseases."

"In addition to their chemopreventative abilities, these molecules might also form the basis of a potent chemotherapy, either alone or in combination with other modes of therapy," said Shibata.

According to Shibata, the next step for the researchers is to further examine the drug delivery mechanisms, toxicology and pharmacokinetics of these analogues, before extending the research to clinical trials. Their studies were funded by the Japanese Society for the Promotion of Science and the Miyagi Health Service Association.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Genome Institute of Singapore
Winnie Serah Lim
(65)9730 7884
limcp2@gis.a-star.edu.sg

American Association for Cancer Research
Staci Vernick Goldberg
(267) 646-0616
Staci.Goldberg@aacr.org

Rare Cancer-causing Syndrome Found, for the First Time, in Singapore

registration@aacr.org () — Sun, 04 Nov 2007 12:00:00 GMT

Findings from the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment Singapore, November 4-8, 2007

SINGAPORE -- A rare hereditary disorder that strongly predisposes carriers to develop cancer at an early age has been found in an Asian female, report researchers today at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine.

Generally, a person should have two normal copies of the powerful p53 tumor suppressor gene. But in the disorder known as Li-Fraumeni syndrome (LFS), one defective copy of p53 is inherited from a parent. Only about 400 families worldwide are known to have LFS, but none had been found in Singapore before this study, say researchers from the National Cancer Centre Singapore.

Although LFS is rare, it was found in a woman who had developed early onset breast cancer. Therefore, clinicians should also consider LFS as a potential diagnosis in young women with breast cancer, say the study investigators, Ann S.G. Lee, D.Phil., of the Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, and Peter Ang, M.Med., of the Department of Medical Oncology, National Cancer Centre Singapore.

"In a selected population of young breast cancer women with a family history suggestive of LFS, genetic testing may help to identify the syndrome," said Lee. "Since LFS greatly increases the risk of developing several types of cancer, it would be important if it could be identified early. This would help persons at risk decide on certain health surveillances and other measures that might improve their long term health."

People with LFS are at increased risk for developing multiple primary tumors of many different origins. In cancer patients who do not have LFS, cancer normally "knocks out" the normal function of p53 in order to grow and metastasize. But when a person only has one working copy of the gene to begin with, the chance that cancer will develop increases significantly, Lee says.

The prevalence of LFS in Singapore is unknown. Because one of the research interests of the National Cancer Centre Singapore is breast cancer susceptibility, investigators there decided to look for evidence of the syndrome in women who developed breast cancer at 35 years of age or younger. About four percent of breast cancer in Singapore is found in younger women, researchers say.

They recruited 30 patients and their families, took detailed family histories and tested their blood for mutations in the p53 gene and the CHEK2 gene, another tumor suppressor gene found to be mutated in some patients with LFS.

They found LFS in one woman in Singapore who had been diagnosed with breast cancer at age 25. Her mother had been diagnosed with breast cancer at age 34, and died at age 35, and a sister died of a brain tumor when she was 10 years old. The patient's non-identical twin sister, determined by DNA fingerprinting, does not have LFS and does not have the p53 mutation found in her affected twin.

The researchers add that establishing a detailed family history that extends back for three generations, which is necessary to make a diagnosis of LFS, can be problematic. "In Singapore, many families are small and many are migrants, and it can be difficult to obtain the needed history," Lee said. "That is why we focused our study on young onset breast cancer patients and tested these individuals for germ-line mutations in the p53 gene."

The study was funded by the SingHealth Cluster Research Fund and the National Medical Research Council of Singapore.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Genome Institute of Singapore
Winnie Serah Lim
(65)9730 7884
limcp2@gis.a-star.edu.sg

American Association for Cancer Research
Staci Vernick Goldberg
(267) 646-0616
Staci.Goldberg@aacr.org

American Association for Cancer Research Announces AACR Asia

registration@aacr.org () — Sun, 04 Nov 2007 12:00:00 GMT

PHILADELPHIA -- The American Association for Cancer Research (AACR) is pleased to announce its plans to facilitate global advances in cancer research through the establishment of AACR Asia, an office that will open officially in Singapore in 2009.

As the world's oldest and largest organization dedicated to the conquest of cancer, the AACR seeks to advance its mission to prevent and cure cancer through research, education, communication and collaborations. In pursuit of this mission over its 100-year history, the AACR has earned a highly regarded reputation for excellence in cancer research and advocacy, and wishes to further its work in the international arena by opening an office in Singapore, a central location in Asia.

Recent trends have made the Asian Pan-Pacific region an attractive and exciting place to engage in cancer science and build upon existing activities of the AACR. Top researchers from around the world are being drawn to the region - to Singapore, in particular - because of the countries' increased support for bioscience research and technology. The AACR commends the governments of Singapore and other Asian Pan-Pacific nations for their unfaltering commitment to advancing bioscience and biomedical research, which has broadened scientific research opportunities across the region and has yielded considerable growth in the number of research centers of excellence. Singapore is a burgeoning center for scientific discovery, with a high demand for leading-edge science, education and training, and with its stellar scientific expertise and international outreach the AACR is poised to enhance collaborations in the region and advance progress against cancer.

Perhaps most importantly, the AACR wishes to address the growing incidence of cancer in the Asian Pan-Pacific region. It is a core belief and value of the AACR that advances in cancer research lead to excellence in the diagnosis, treatment and prevention of cancer. The time is right for the AACR to leverage the region's growth trends in cancer research and funding to advance cancer research globally, which ultimately will translate new knowledge into better cancer care and cures for all humankind.

Specifically, the AACR establishes AACR Asia to:

Become a global hub for cancer research information, networking and collaborations;
Increase cancer research collaborations between the East and West;
Provide educational opportunities for young scientists in the Asian Pan-Pacific region;
Boost AACR's insight into cancer and cancer research in the Asian Pan-Pacific region and thus serve as an expert resource in the region;
Facilitate and influence cancer public health and cancer research policy in the region;
Further develop collaborations with regional governments, universities, and international non-governmental organizations;
Identify new development and funding opportunities for cancer research.

The AACR is pleased to demonstrate its commitment to expanding its presence in Asia by hosting the first AACR Centennial Conference, Translational Cancer Medicine: From Technology to Treatment, this week in Singapore. This special meeting will convene an international group of senior scientists, young investigators and physicians from academia, industry and government to present new and developing technologies that will enable the translation of basic cancer research into the practice of cancer medicine. From this first step, the AACR will continue to develop relationships with key stakeholders from various sectors in the region and create an advisory committee with the goal of opening an office in Singapore in 2009.

The AACR wishes to thank the Government of Singapore, Minister of Health Mr. Boon Wan Khaw, Dr. Edison T. Liu and the Genome Institute of Singapore and A*STAR for their assistance in and support for its expansion into the Asian Pan-Pacific region.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Staci Vernick Goldberg
267-646-0616
staci.goldberg@aacr.org

Emerging Therapies with a Focus on Asian Populations Mark the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment

registration@aacr.org () — Thu, 01 Nov 2007 12:00:00 GMT

Singapore on November 4-8, 2007

SINGAPORE -- To mark its 100th year of advancing cancer research, the American Association for Cancer Research is holding Centennial Conferences in North America, Europe, and Asia. The AACR has teamed with the Genome Institute of Singapore and Singapore's Agency for Science, Technology and Research (A*STAR) to hold the first of these conferences from November 4 to 8 in Singapore: the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment.

The conference will convene cancer research experts, scientists in training, and physicians from academia, industry, and government in Singapore to discuss emerging technologies that will enable the translation of laboratory discoveries into the practice of cancer medicine.

"This meeting will foster the necessary dialogue to speed application of breakthrough laboratory discoveries to the practice of medicine. Translational cancer medicine provides the tools to build the connections needed to move practical knowledge from the laboratory to drug development to patient care," said William N. Hait, M.D., Ph.D., president of AACR, co-chairperson of the conference and senior vice president and head, worldwide hematology oncology research and development at Johnson and Johnson. "By hosting this meeting in Singapore, not only are we expanding this discussion across international lines, but we are also highlighting the unique strengths of our Singapore colleagues as well as the challenges faced by researchers in response to the needs of Asian patients."

Specific topics will include advanced studies in cancer biology, genomics and molecular targets for future cancer drugs as well as the latest imaging, and high-throughput approaches to cancer detection, diagnosis, and treatment. The meeting will also explore questions specific to the region, such as the constraints and opportunities of cancer care delivery in Asia, and how best to tailor cancer treatment to the genetic profile of tumors found among Asian populations.

"The early years of the 21st century no doubt will go down in history as a turning point in our efforts to improve the prevention and treatment of cancer through knowledge gained in the laboratory," said Edison Liu, Ph.D., executive director of the Genome Institute of Singapore, one of the 14 research institutes in the A*STAR collaborative. "Translational research has become one of the most exciting areas of science at every major biomedical institution, from Singapore to Boston to London."

# # #

Contact:
Genome Institute of Singapore
Winnie Serah Lim
(65)9730 7884
limcp2@gis.a-star.edu.sg

American Association for Cancer Research
Staci Vernick Goldberg
(267) 646-0616
Staci.Goldberg@aacr.org

Targets on the Horizon: Emerging Therapies and Novel Targets

registration@aacr.org () — Thu, 25 Oct 2007 12:00:00 GMT

SAN FRANCISCO - What are the cancer drugs of tomorrow and how will they be developed? Today, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, researchers will present some answers to these and other pressing questions regarding emerging cancer therapeutics.

New targets, such as cell signaling receptors found on cancer tumors, provide tantalizing targets for engineered antibodies and small inhibitory molecules. New therapeutic technologies, such as virus-based therapy against cancers metastasized to nerve cells and a unique two-headed antibody that attaches killer T cells to tumor cells, offer promising methods for controlling disease.

Preclinical anticancer properties of potent small molecule inhibitors of protein kinase D: Abstract A 237.

A team of researchers from Cancer Research Technology based at University College London report for the first time CRT0059359, a small molecule inhibitor of protein kinase D (PKD), a key part of a chemical signaling pathway that is disrupted in a variety of cancers, including pancreatic cancer.

Thought to be involved in a number of cellular processes, PKD plays a vital role in cell division signaling leading to tumor cell proliferation, and in apoptosis, or programmed cell death.

"We think this is the first viable protein kinase D inhibitor that has come to light - and our studies using this molecule validate protein kinase D as an anti-cancer target," said lead researcher Lloyd Kelland, Ph.D., D.Sc., head of biology at Cancer Research Technology. "In cell and animal models of pancreatic cancer, this particular molecule appears to effectively induce apoptosis."

According to Kelland, their previous studies demonstrated that blocking the gene that produced PKD drastically reduced the survival of a human pancreatic cell culture. To find an effective inhibitor for PKD, the researchers initially screened over 65,000 molecules to determine if any of them blocked the function of the protein.

Following chemical refinement of molecules found in the screen, only CRT0059359 had the appropriate chemical properties for testing for anticancer activity in animal models of cancer.

Exposure of pancreatic cells to CRT0059359 showed a marked decrease in cell proliferation and increase in apoptosis. Studies using a mouse model of pancreatic cancer indicated that CRT0059359 demonstrates a reasonable reduction of tumor growth without causing harm to healthy cells. "More importantly, this particular molecule isn't our final candidate, yet, as we are refining its chemical structure to improve bioavailability and increase potency," Kelland said.

Nerve-sparing therapy with oncolytic herpes virus for cancers with neural invasion: Abstract PR 8.

A cancer-targeting herpes virus could effectively stop the spread of cancer to the nervous system, preventing paralysis according to a report presented by researchers from Memorial Sloan-Kettering Cancer Center. Their study, funded by the National Institutes of Health, demonstrates that the oncolytic (cancer-killing) virus is safe in an animal model of human cancer and selectively targets cancer cells without damaging nerves.

Neural invasion, the movement of metastasized cancer into nerves, is a debilitating feature of many forms of spreading cancer, especially in prostate, head and neck, and pancreatic carcinomas. Treatment for neurally invasive cancer includes resection - the physical removal of the cancer cells through surgery - which often damages the nerve, leading to loss of function. Approximately 25 percent of all prostate cancers cases, for example, spread to nerves, and surgery to remove them often leads to erectile dysfunction and incontinence.

"The invasion of cancer cells along nerves is generally linked with poor outcomes for patients, and can have awful consequences for patients even when it is successfully treated," said Ziv Gil, M.D., Ph.D., a researcher at Memorial Sloan-Kettering Cancer Center. "By modifying a virus that is naturally attracted to nerves, it can serve to target and kill cancer and prevent healthy nerves from being damaged."

In the study, Dr. Gil and his colleagues worked with a genetically engineered herpes simplex virus called NV1023, which had been rendered non-virulent by removing the gene that allows the virus to attack healthy cells. For reasons that are still not entirely clear to researchers, the virus is lethal to cancer cells, despite the fact that it ignores healthy tissue.

The researchers demonstrated that the virus effectively killed cells from three human carcinoma cell lines: pancreatic, head and neck, and prostate cancer. In addition, using a novel animal model, the researchers demonstrated that a single injection of an attenuated (non-virulent) herpes virus can effectively treat nerves infiltrated by cancer, while preserving physiological nerve function. Remarkably, all of the un-treated animals with cancers developed complete nerve paralysis within five weeks, whereas most of the NV1023 treated animals had intact nerve function up to 14 weeks after treatment. Phase I studies of the attenuated virus in humans are underway.

AR36A36.11.1, a monoclonal antibody targeting CD59, enhances complement activity and exhibits potent in vivo efficacy in multiple human cancer models: Abstract A 70.

Scientists at ARIUS Research, Inc., a biotechnology company based in Toronto, Canada, have discovered a potential therapeutic that foils cancer cell's ability to hide from the immune system. According to their findings, the antibody, termed AR36A36.11.1, allows the immune complement system - protein complexes that recognize and kill foreign cells - to target and kill tumors by rupturing their membranes. AR36A36.11.1 activates complement activity against cancer cells and inhibits tumor growth in mouse models of breast, colon, lung and prostate carcinomas, the researchers say.

"While tumors can present markers that indicate they are diseased, they often evade the innate immune system by producing an excess of CD59, a surface protein that prevents the assembly of complement proteins on the outside of tumor cells," said Baldwin Mak, Ph.D., a research scientist at ARIUS. "Through the inhibition of CD59, we can disrupt a cancer cell's ability to keep the immune system from poking holes in its membrane."

According to Mak, the CD59-inhibiting antibody was discovered through a technique developed at ARIUS called "FunctionFIRST^TM," a methodology that screens antibodies for cell killing effects rather than creating antibodies that bind a specific target. After AR36A36.11.1 proved effective at killing cultured cancer cells, the researchers tested the molecule in animal models of adenocarcinomas. "Subsequent analyses revealed the mechanism of action - the antibody binds to a region on CD59 that inhibits formation of membrane attack complexes, which form pores that cause cell lysis," said Mak.

When administered in mice once a week for eight weeks, AR36A36.11.1 inhibited breast cancer tumor growth by 100 percent. Mouse studies also revealed that the antibody could halt the growth of prostate tumors by 86 percent, lung tumors by 58 percent and colon tumors by 48 percent, said Mak.

"Our studies seem especially promising in breast cancer models, where CD59 inhibition by the antibody appears to cause complete tumor regression at all dose levels," said Mak. In particular, this potent effect is observed in a breast cancer model that represents a patient population that cannot be treated by Herceptin, the only therapeutic antibody approved for breast cancer treatment.

A humanized AR36A36.11.1, suitable for clinical studies, has been made and the researchers are preparing to test this antibody in clinical trials.

AR47A6.4.2, a functional naked monoclonal antibody targeting Trop-2, demonstrates in vivo efficacy in human pancreatic, colon, breast and prostate cancer models: Abstract PR 12.

A newly generated antibody has been found to be effective against an array of human cancers -including those of the pancreas, colon, breast and prostate - report researchers from ARIUS Research, Inc., a biotechnology company based in Toronto, Canada.

According to the researchers, the antibody, AR47A6.4.2 targets Trop-2, a protein found on the surfaces of cells and thought to be a key part of the expansive MAPK pathway, an enzymatic cascade crucial for the control of a cell's life cycle.

ARIUS researchers report that the antibody has a significant anti-tumor effect in a mouse model of human pancreatic cancer, greatly extending the lifespan of the mice. Subsequent testing showed efficacy in mouse models of breast, colon and prostate cancers. The antibody inhibited tumor growth by 100 percent in a pancreatic cancer model, 90 percent in a breast cancer model, 60 percent in a colon cancer model and 61 percent in a prostate cancer model, the researchers report.

"Trop-2 is a novel target - a protein that has been implicated in the cancer literature as related to very aggressive cancers, but its exact function has not been clear," said Amandine H.L. Truong, Ph.D., a research scientist at ARIUS.

According to Truong, the antibody that bound to Trop-2 was discovered through a technique developed at ARIUS called "FunctionFIRST^TM," a process that works in reverse of traditional methods for generating antibodies. Most research in targeted therapeutics involves generating antibodies based on known targets. Through the ARIUS method, researchers generate effective antibodies first, by screening them against cancer cell samples to select the most potent ones. Only through later analysis do they discover the exact targets of the antibodies.

ARIUS researchers are currently preparing for clinical trials with a "humanized" form of the antibody.

Highly efficient elimination of melanoma cells expressing melanoma-associated chondroitin sulfate proteoglycan (MCSP) by MCSP/CD3-bispecific chain antibody constructs: A 61.

An engineered antibody-like molecule that binds skin cancer cells to killer T cells, literally tying melanomas to the immune system, could provide a novel therapy for the disease, according to researchers at Micromet, a biotechnology company based in Bethesda, Md., and Munich, Germany. Melanomas are particularly sensitive to T-cell therapies, the researchers say, and their novel antibody construct could be a means of engaging some of the most effective cancer-killing cells in the immune system's arsenal.

These agents are new class of artificial antibodies - what Micromet researchers term a BiTE class (for bispecific T-cell engager) - that are T cell-recruiting antibodies. Essentially, the researchers have linked the binding regions of two specific antibodies together with a short peptide chain.

In this case, one antibody binds to an activating receptor on the surface of killer T cells, called CD3, and the other binds to a protein generally found on the surfaces of skin cancers, called melanoma-associated chondroitin sulfate proteoglycan (MCSP).

"Unlike regular monoclonal antibodies used in cancer therapies, BiTE antibodies can recruit killer T cells for redirected lysis of tumor cells," said Roman Kischel, M.D., director of immunotherapy at Micromet. "By this approach only cells expressing the antigen are attacked by T cells, and we can see target cell lysis at very low picomolar concentrations of BiTE antibodies."

When MCSP-BiTE binds to cancer cells, the cells become visible for any killer T cell passing by. "The T cell will briefly attach to the BiTE-decorated cancer cell and inject its deadly cocktail of killer proteins into the tumor cell," Dr. Kischel said. "This event gears up the T cell to produce more killer proteins and to go into melanoma serial killing mode."

According to Dr. Kischel, the BiTE antibodies do not require specific killer T cells, which may circumvent many limitations of T-cell therapies, such as the mechanisms that some tumors use to escape the immune system and defects in the ability of immune cells to recognize antigen, a frequent problem among cancer patients. Even on the cellular scale, BiTE antibodies are tiny, about a third of the size of conventional antibodies, which Micromet researchers believe may aid by improved tumor penetration in the effectiveness of the therapeutic.

Currently, Micromet researchers are studying similar antibodies specific for B-cell lymphomas in a Phase I trial. The MCSP-BiTE antibodies are now undergoing preclinical studies in cell cultures and animal models.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

The National Cancer Institute, founded in 1971, is the principal United States government agency charged with coordinating the National Cancer Program. It facilitates international cooperation in clinical trials involving U.S. and foreign collaborating institutions.

The European Organisation for Research and Treatment of Cancer is an international non-profit research organization created in 1962. The mission of the EORTC is to conduct, develop, coordinate and stimulate translational and clinical research in Europe, and to improve the management of cancer and related problems by increasing the survival and quality of life for patients.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In San Francisco (10-22-10/16):
415-348-4521

Experimental Cancer Pharmaceuticals under Trial

registration@aacr.org () — Wed, 24 Oct 2007 12:00:00 GMT

Highlights from the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

SAN FRANCISCO - Advances in drug development have enabled scientists to attack new and unconventional cancer targets, leading to better treatments for cancer patients with fewer unwanted side effects. The following items highlight the early results from two experimental therapeutics, currently involved in Phase I or II trials, which are being presented today at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

A potent and selective inhibitor of the mitotic kinesin CENP-E (GSK923295A) demonstrates a novel mechanism of inhibiting tumor cell proliferation and shows activity against a broad panel of human tumor cell lines in vitro: Abstract A 111.

A first-in-class, targeted investigational therapy specifically designed to inhibit a single protein that functions only during cell division shows potent activity in a broad range of cancer cell lines, say researchers from GlaxoSmithKline. Because the compound is so specifically targeted, it may help reduce some of the more common toxic side effects of chemotherapy, they say.

The experimental drug, GSK923295A, inhibits the mitotic kinesin centromere-associated protein E (CENP-E), which is required during mitosis, the process by which a cell duplicates its genetic information in order to generate two, identical, daughter cells. The resulting mitotic arrest can lead to apoptosis, or cell death. A characteristic of CENP-E inhibition is the presence of misaligned or lagging chromosomes within cells attempting to replicate.

"Investigators were able to observe lagging chromosomes in most tumor cells treated with GSK923295A. These effects are rarely observed in untreated cells," said the study's lead investigator, David Sutton, B.Sc., associate director of biology, within the Oncology division of GlaxoSmithKline in Collegeville, Pa. GlaxoSmithKline funded the study.

Although CENP-E is expressed in all dividing cells, GSK923925A is more likely to affect rapidly dividing cancer cells, Sutton says. Furthermore, because of the very low expression of CENP-E in non-dividing cells such as neurons, GSK923295A may not cause the peripheral nerve damage often seen with chemotherapy treatments such as taxanes and vinca alkaloids, which also inhibit mitosis, he says.

Studies conducted in animal models have shown complete tumor regression in some cancer types, says Sutton. In preclinical tests conducted in 214 solid and 85 hematological tumor cell lines, sensitivity to GSK923295A was seen in 16 out of 17 breast tumor cell lines, 20 out of 25 colon cancer lines, 24 out of 26 lung cancer lines, 11 out of 11 ovarian cancer lines, and six out of six prostate cancer lines, he says. Additionally, laboratory analysis suggests that anti-tumor activity might be achieved with minimal suppression of the bone marrow, which could reduce the typical myelosuppression (reduction in production of blood cells) seen with chemotherapy treatment, he says.

"It is a big leap from doing laboratory experiments to understanding what will happen in patients, but we think it is very encouraging that this first-in-class drug candidate shows both broad activity and the potential for enhanced tolerability in preclinical studies," Sutton said. GSK923295A, a small molecule drug given intravenously, is now being evaluated in a Phase I clinical trial in patients with advanced solid tumors. It was discovered and optimized by GSK, in partnership with Cytokinetics Inc.

Phase I pharmacokinetic study of ECO-4601, a novel bifunctional targeting agent: Abstract B 119.

Researchers report positive results from a Phase I/II clinical trial of a novel anti-cancer drug which offers two modes of action. In 26 patients with advanced solid tumors, treatment with ECO-4601 is safe and well tolerated, including at doses yielding plasma concentrations above the expected therapeutic threshold, says Pierre Falardeau, Ph.D., chief operating officer at Thallion Pharmaceuticals in Montreal, Canada. Thallion has produced and tested ECO-4601 in association with the Segal Cancer Centre of McGill University.

Falardeau says that ECO-4601 has a unique mechanism of action comprising two distinct activities. It inhibits the RAS/MAPK intracellular signaling pathway, which is mutated in many cancer types, and which is the target of several approved cancer drugs such as Erbitux, Avastin, Tarceva, Nexavar, and Sutent. "However, unlike these drugs, our preclinical experiments suggest that ECO-4601 acts at a unique point within the pathway, specifically at the level of RAS itself," Falardeau said.

As a target for inhibition, RAS presented researchers with a chance to affect the signaling pathway with less fear that loops in the pathway will compensate for its loss. "Because RAS sits at a crossroad of multiple signaling pathways, targeting RAS may avoid some of the redundancies inherent in intracellular signaling," Falardeau said.

The agent also binds to the peripheral benzodiazepine receptor (PBR), which is over-expressed in multiple cancers. This intracellular PBR binding may allow the drug to accumulate within tumor cells, providing a more efficient way to inhibit the RAS/MAPK signaling pathway. "In other words, ECO-4601 may preferentially target and accumulate within tumor cells because of the over-expression of the PBR," Falardeau said.

In addition to its safety, the researchers also found that, while blood concentrations of the drug increased linearly along with an increase in dosage, at the end of the treatment's two-week infusion, ECO-4601 was cleared from the blood relatively quickly. "Therefore, there is unlikely to be drug accumulation from cycle to cycle. This is important as the drug is intended to be used chronically and if a drug accumulates, side effects and toxicities may develop," Falardeau said. The anti-tumor activity of ECO-461 is further maximized by continuous infusion, he explains.

The researchers say that of seven patients who completed three cycles of drug treatment in the dose escalation portion of the trial, six demonstrated stable disease, which Falardeau suggests is a preliminary sign of efficacy. "These data, together with extensive non-clinical data and the data presented at this conference, support the continued development of ECO-4601 for the treatment of cancer," said Falardeau.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In San Francisco (10-22-10/26):
415-348-4521

A Fresh Look at Existing Therapies: Researchers Explore Ways to Teach Approved Drugs New Tricks

registration@aacr.org () — Wed, 24 Oct 2007 12:00:00 GMT

SAN FRANCISCO - Although all cancers are not alike, most share common causes, whether it is the result of a genetic mutation or faulty biochemical signaling pathway. For that reason, drugs developed specifically for one disease might have an impact on many others. Increasingly, researchers are discovering ways of combining new and existing drugs to fight cancer - broadening the targets of already-approved targeted therapeutics.

Today at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, researchers present the results of some of these investigations, whether it is finding a new use for the immunosuppressant rapamycin or adapting the use of approved antibodies to reach the same targets within different cancers.

Combination of CP-751871, a human monoclonal antibody against the IGF-1 receptor, with rapamycin results in a highly effective therapy for xenografts derived from childhood sarcomas: Abstract C172.

Researchers at St. Jude Children's Research Hospital in Memphis, Tennessee, have discovered that an engineered antibody, in combination with rapamycin, may offer treatment for rhabdomyosarcoma, osteosarcoma, and Ewing's' sarcoma -- three rare childhood cancers. The antibody, called CP-751871, is currently in a Phase III trial by its developer, Pfizer, Inc., while rapamycin, an approved immunosuppressant, is also under study for its anti-cancer properties.

Combined, the researchers believe, the two therapeutics act in a way that helps to promote apoptosis, a series of internal signals within a cell that cause its self-destruction. CP-751871 binds to - and thereby blocks the action of - a cell surface protein called insulin-like growth factor receptor (IGF-1R), which research has shown to be a part of a process that limits apoptosis. Rapamycin has been shown to inhibit mTOR, a protein involved in regulation of cell growth, proliferation and survival. There is increasing evidence that activation of cellular proteins upstream or downstream of mTOR is critical in the process of cancer progression.

"Together, the two therapeutics seem to have a synergistic effect in human sarcomas, combined they function more strongly than either drug alone," said Raushan T. Kurmasheva, Ph.D., a post-doctoral fellow at St. Jude. "We are looking to extend our studies to include more sarcoma models, but we believe this looks like a promising clinical application for these drugs."

According to Kurmasheva, the combined therapy could be a breakthrough in treatment of human sarcomas in general and childhood sarcomas, in particular. Both Ewing's sarcoma and osteosarcoma are cancers of the bone and connecting tissue that are most frequently diagnosed in teens. Rhabdomyosarcoma is a rare disease that primarily affects children between the ages of one and five, but which can also strikes adolescents. While prognosis for childhood sarcomas is generally good, if caught early, children with these diseases face a grim prognosis if the cancer metastasizes, Kurmasheva says.

With support from the National Cancer Institute and Pfizer, the St. Jude researchers began their study in cell cultures of both cancer types. The antibody, alone, significantly retarded cell growth, they found. In animal models of sarcoma, both drugs curbed tumor growth. The two drugs combined, however, induced complete regression of established tumors. Due to the encouraging results, Kurmasheva and her colleagues are looking to expand their research to other animal models as well as look for biomarkers that could indicate positive response to treatment in a clinical setting.

Therapeutic effects of the anti-CD74 mAb, milatuzumab, compared to anti-CD20 antibodies, in B-cell lymphomas: Abstract: A 58.

If one monoclonal antibody has revolutionized treatment of B-cell lymphoma, then two might offer even more benefit, according to researchers at Garden State Cancer Center based on their findings in preclinical animal studies.

The current standard of care is rituximab, a drug that targets CD20, a protein receptor that is highly expressed on the surface of lymphoma cells. Half of patients with B-cell lymphoma do not respond to rituximab, however, and those who do eventually relapse. Therefore, according to researchers, the search is on for other antibodies to add to rituximab to increase its efficacy.

Use of an agent called veltuzumab, an anti-CD20 antibody currently under development, along with milatuzumab, an experimental antibody that targets a different receptor called CD74, significantly improved survival in mice who received the monoclonal antibody treatment cocktail, the Garden State team reports. Using mouse models of B-cell lymphoma, they found that treatment with veltuzumab extended median survival time from 36 days in untreated mice to 70 days, and milatuzumab extended median survival time to about 90 days. However, when both agents were used, mice lived a median of 113 days.

"The important finding is that we show that using a combination of two antibodies targeting two different receptors on the malignant cells, when the receptors have different functions, leads to an improvement in survival over use of either antibody alone," said Rhona Stein, Ph.D., of the Center for Molecular Medicine and Immunology's Garden State Cancer Center.

"This also suggests that if the malignant cells become refractive to one antibody, the other may still be effective, since it can bind to a different receptor," she said.

Both veltuzumab and milatuzumab are "naked" antibodies - monoclonal antibodies that are not bound to a therapeutic drug or radioisotope - but each latches on to different receptors on the surface of lymphoma cells.

Milatuzumab binds to the CD74 receptor and is then rapidly internalized into the cell, in contrast to CD20, which is not taken inside cells as rapidly. "The CD74 receptor is known to process antigens as part of the immune response, and recently was shown to be a survival factor in certain malignant cells, chronic lymphocytic leukemia," she said. "So it appears to have a dual function, and the latter seems to make it an attractive candidate for antagonistic CD74 antibodies."

Veltuzumab is a second-generation humanized anti-CD20 antibody now in clinical testing, which works very similarly to rituximab, except that lower doses and shorter infusion times can be used, Stein says. Both of the drugs tested in this study, milatuzumab and veltuzumab, were developed by Immunomedics, Inc. Stein and her colleagues were funded through grants from the National Cancer Institute and the New Jersey Department of Health and Senior Services

These preclinical studies suggest benefit in testing the combination in patients, Stein says. "We believe that combination antibody therapy, just as combination chemotherapy, will be the future for antibody-based immunotherapy," she said.

Neoadjuvant clinical trials for biomarker discovery: An old idea to solve a new problem: Abstract A229.

With the recent approval of four new agents and more coming through the drug development pipeline, treatment of advanced common kidney cancer has become a multiple choice decision of late - but one without a definitive answer. Physicians say they have no rational way to decide which drugs or drug combinations would work best for patients with renal cell carcinoma, especially those whose cancer has recurred and spread.

Now, researchers at the University of North Carolina at Chapel Hill are adapting the idea of neoadjuvant therapy - treating cancer before surgery - to renal cell carcinoma. Their intent is to use a short course of treatment to evaluate the performance of the new drugs across populations of patients, and preliminary results are promising, the researchers say. Sorafenib, sunitinib, and temsirolimus were all approved for use in renal cell carcinoma within the last two years.

"Neoadjuvant therapy is an old idea, with the primary intent to downstage a tumor and increase the likelihood of successful surgical resection. We are using it to extract biomarker information on efficacy of treatment instead," said W. Kimryn Rathmell, M. D., Ph.D., of the Division of Hematology/Oncology at the Lineberger Comprehensive Cancer Center.

In this study, researchers measured patients' tumor responses to a short course of treatment before surgery using CT imaging, and analyzed potential biomarkers using functional imaging with PET imaging, blood and urine analysis before and after treatment, and the regulation of genes and proteins within the tumor.

Their first results, evaluating 4 to 8 weeks of sorafenib in 30 patients prior to surgery is currently under analysis. Early results show that among 10 of the 30 patients, the average response is a 10 percent reduction in size of the primary tumor, with a range between 0.8 percent and 28 percent. No tumor progression has been observed in any of the patients, and no unexpected surgical complications have been observed, Dr. Rathmell says.

Treating advanced renal cell carcinoma is difficult because results from clinical trials of new agents in advanced disease are difficult to interpret due to lack of good biomarkers, Dr. Rathmell says. "This is because there is limited access to tumor tissue acquired at or around the time of the treatment, the influence of prior therapy received by patients, and the relative co-morbidities these patients have compared to newly diagnosed patient," she said.

Additionally, no genetically engineered mouse models have been validated for renal cell carcinoma, Dr. Rathmell says. "Conventional xenograft studies, growing human tumor cells in an immunocompromised mouse fail to account for many of the tumor and host factors that influence tumor growth in humans, such as the absence of immune surveillance and an imperfect host environment for tumors," she said.

"The idea is to use a window of opportunity not traditionally explored to examine therapeutic biomarkers, and to identify subpopulations of patients who will derive a predictable higher likelihood of response from a given agent that is now available," Dr. Rathmell said. "Patients proceed to surgery regardless of the response to the very short course of treatment."

Due to scheduling constraints, the following presenter will not be available for the press briefing. Dr. Antonio Jimeno will be available for interviews with reporters from 1 p.m to 3 p.m. PST and again from 4 p.m. to 7 p.m PST on Wednesday, October 24.

Coordinated over-expression of genes in the EGFR pathway predicts sensitivity to EGFR inhibition in pancreatic cancer: Abstract B 108.

Researchers at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center working in preclinical models of pancreatic cancer have found a way to identify those patients most likely to benefit from Tarceva (erlotinib), which has been approved for use in the disease but whose overall efficacy they seek to improve. Using a gene-expression-based tool to look for pathways involved in pancreatic cancer, they matched response to Tarceva to activation of the EGFR pathway which the drug targets.

"Identifying the subset of patients that benefits the most from Tarceva is a priority, and this method appears to offer us a way to do that," said Antonio Jimeno M.D, Ph.D., a researcher in the Gastrointestinal Cancer Program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.

"Of course this is preliminary preclinical data, but the model we used is based on direct patient xenografts and not cell lines, and we have reasons to believe this system is more representative of cancer biology."

Many cancers rely on what scientists call "oncogene addiction," which refers to malignant processes that are driven by a single alteration, such as mutations in the EGFR gene in lung cancer or over-expression of HER2 in breast cancer. "Therapies have been successfully developed targeting those key alterations, turning the presence of the abnormality into a hallmark of activity, or a predictive biomarker," Dr. Jimeno said.

But the Hopkins researchers, led by Manuel Hidalgo, M.D., Ph.D., suspected that pancreatic cancer - a disease in which EGFR-targeted therapies have proved to be of use, but where amplifications or mutations in the EGFR gene are rare - is an example of a cancer driven by "pathway addiction." The problem, however, is that no one knows what the determinant of Tarceva activity is in pancreatic cancer, Jimeno says.

The team used a tool known as gene set enrichment analysis (GSEA), which classifies 25,000 genes assayed in a chip into 198 predetermined pathways, be they metabolic, structural, or signal transduction. This analysis was conducted by Aik Choon Tan, Ph.D., from the Institute of Computational Medicine at Johns Hopkins. The researchers looked at messenger RNA levels to determine which pathways were more actively expressed in patients whose disease responded to Tarceva. Two of the most frequently expressed pathways in Tarceva-sensitive cases were the closely related EGFR and MAPK pathways, they found.

"What we did that was different is that rather than examining gene expression datasets looking for outliers or individual genes, we employed GSEA to detect modest but coordinated changes in expression of genes involved in a common pathway or biological function," Dr. Jimeno said.

They then validated the prediction in a prospective cohort of patient-derived tumors xenografted on mice that were treated with Tarceva, and found that the EGFR pathway was again highly expressed in Tarceva-sensitive tumors compared to resistant tumors, and the EGFR pathway signature predicted anti-EGFR treatment response in this second group of tumors.

"We are excited because this reinforces the notion that targeted agents work in cases where the target is relevant," Dr. Jimeno said. "We only need to take into consideration the enormous intricacy of cancer and use tools that permit us to factor in that complexity."

Dr. Jimeno adds this finding offers some good news in this difficult-to-treat cancer. "GSEA or another tool like it might help us down the road to tailor anti-EGFR therapy to those patients most sensitive to it, and it also provides an alternative, more integrative way to think about how to look for pathways that are relevant in cancer," he said.

Dr. Jimeno and his colleagues were supported in part by an American Society of Clinical Oncology Young Investigator Award to Antonio Jimeno, the Sol Goldman Center for Pancreatic Cancer Research, the Viragh Family Foundation and the Lee family.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In San Francisco (10-22-10/16):
415-348-4521

Combination Targets: Some Drugs May Work Best When They Work Together

registration@aacr.org () — Wed, 24 Oct 2007 12:00:00 GMT

SAN FRANCISCO - While some targeted therapies - drugs developed to attack specific molecules in the critical chemical pathways occurring within cancer cells - work well by themselves, increasingly researchers are finding that they work better when teamed with other targeted and conventional therapies.

Reported today at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, multiple-target applications of new and existing drugs are offering new hope in the fight against cancer and drug resistance, from lung and breast cancer to rare tumors of the bile duct.

Synergistic effects of multi-level targeting of the MAPK and PI3-kinase pathways in breast cancer cells: Abstract B 128.

The chemical signaling pathways that control the life cycle of cells offer many important targets for cancer researchers hoping to stop the growth of tumors, yet the complex nature of these pathways may make it impossible to kill a cell with a single therapeutic bullet, as researchers from the University of California, San Francisco, (UCSF) have discovered in a study of breast cancer cells. Their findings suggest that molecules used to inhibit the MEK protein, similar to those being studied to control breast cancer growth, can "switch on" another pathway that keeps cancer cells from dying.

Their solution is to look elsewhere to see where these pathways intersect, which has allowed them to uncover two targets that, when chemically inhibited at the same time, caused apoptosis -cell suicide. This combination therapy approach might make it difficult for cancer cells to resist the disruption of a single protein along a particular signaling pathway.

"The chemical networks involved in cell cycle control have a tendency to be much more complicated than we initially expect, with intersecting pathways and feedback loops," said Michael Korn, M.D., an associate professor in residence at the UCSF's Comprehensive Cancer Center. "To understand the connections between these pathways we have taken a systems biology approach, one that may uncover new anti-cancer drug targets on different levels within connecting pathways."

As part of a multi-institutional research effort funded by the National Cancer Institute's Integrative Cancer Biology Program, Dr. Korn and his colleagues at UCSF, Lawrence Berkeley National Laboratories and The University of Texas M. D. Anderson Cancer Center are creating computer models informed by their systemic approach that will enable them to identify important proteins within the signaling networks. "There are so many different components involved, that modeling these pathways is as complicated as creating computer models that accurately predict the weather," Dr. Korn said.

The MEK protein is an enzyme involved in the well-studied RAS pathway, which plays a central role in promoting cell growth and multiplication. When not functioning properly, this pathway has been implicated in a number of cancers, Dr. Korn says, including breast cancer. When the researchers treated breast cancer cells with molecules designed to bind to and inhibit MEK, named U0126 and CII040, they observed that instead of dying, the cells simply froze at a single point in their life cycle.

While U0126 and CII040 prevented breast cancer cells from growing, they did not kill the cells implying that some breast cancer cells would survive treatment with MEK inhibitors, Dr. Korn says. In analyzing the performance of the MEK inhibitors, researchers noticed that a similar pathway, identified by the activity of an enzyme called PI3-kinase, had been activated. "So, of course, we decided that we would try blocking the PI3-kinase pathway as well, assuming that simply blocking both pathways would work," Dr. Korn said.

However, combining the MEK inhibitors with a PI3-kinase inhibitor resulted in cells even more steadfastly resolved to stay alive.

"That is when we decided to look elsewhere along the MEK and PI3-kinase pathways, eventually trying MEK inhibitors in combination with a number of inhibitors along the PI3-kinase pathway," Dr. Korn said. "The resulting studies show that, with the select combination of targets, we can elicit a synergistic effect between anti-cancer drugs that are much stronger than either drug's effect alone." Dr. Korn concludes the key to ultimate MEK inhibition may be to bypass the MEK pathway altogether. The researchers found that targeting PI3-kinase and a protein farther down the pathway, called TOR, caused apoptosis in the breast cancer cells. One molecule known to inhibit TOR is rapamycin, an immunosuppressant whose anti-cancer effects are under study. Dr. Korn and his colleagues are currently studying the combination in other breast cancer cell lines in anticipation of later clinical trials.

AZD6244 (ARRY-142886), a potent and highly selective MEK1/2 inhibitor, demonstrates anti-HIF properties, and increases the therapeutic response in a lung tumor xenograft model when combined with radiotherapy: Abstract A 244.

Researchers at the University of Manchester have found that a therapeutic currently in Phase II clinical trials is more effective at shrinking tumors when combined with radiotherapy. In a mouse model for human lung cancer, AZD6244 may increase the potency of radiotherapy by shutting down the cellular machinery that allows cancer cells to cope with a lack of oxygen, a state called hypoxia, they report.

AZD6244 is a small molecule inhibitor developed by AstraZeneca to bind to and inhibit MEK1 and MEK2 proteins, which together form a critical point on the pathway that controls the ongoing survival of cells. Defects along the pathway can lead to increased cell proliferation and cancer, and the drug was developed to halt this important route toward tumor progression.
"The MEK proteins are also part of the pathway that controls the production of HIF-1, the hypoxia-related protein involved in stabilizing cells in the absence of oxygen," said Aoife M. Shannon, Ph.D., a postdoctoral fellow at the University of Manchester. "Furthermore, HIF is associated with protecting tumors from the effects of radiation"

As a cancer treatment, radiotherapy, which works by damaging DNA with ionizing radiation, is relatively less effective against tumors that are deprived of oxygen, or hypoxic, the researchers say. As tumors grow into large masses, they strain the available supply of oxygen and exist in a hypoxic state.

Shannon and her colleagues studied the combined effects of radiation and AZD6244 on human lung cancer cell cultures and a mouse model of human lung cancer, in studies funded by AstraZeneca. In mice they found that the combination of radiotherapy and drug was more effective than either therapy alone. While the drug alone and the combination therapy caused the tumors to shrink to nearly a third of their original volume within 10 days, regrowth took significantly longer in the combination group than in the drug- or radiation-only groups.

According to Shannon, their findings support further development of AZD6244 and radiotherapy as combined regimen, and indicate a novel role for AZD6244 in inhibiting the tumor hypoxia response.

"It is possible that the effect of AZD6244 on HIF as well as tumor blood vessel growth induced by HIF contributed towards the remarkable effects of the combination," Shannon said. "It is a double-pronged approach that will likely be relevant to ongoing trials of MEK inhibitors and inform future studies."

Identifying strategies to enhance responses induced by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas: Abstract A 248.

Researchers at Memorial Sloan-Kettering Cancer Center have developed a strategy to enhance tumor response in some lung cancer patients treated with the tyrosine kinase inhibitor (TKI), erlotinib, by combining it with ABT-737, a small molecule drug that primes tumor cells to undergo apoptosis, or programmed cell death.

"About ten percent of tumors from lung cancer patients harbor mutations in the kinase domain of the epidermal growth factor receptor (EGFR) gene, and these mutations are associated with increased sensitivity to EGFR TKIs." said Yixuan Gong, Ph.D., a post-doctoral researcher at Memorial Sloan-Kettering. "EGFR TKIs, while certainly beneficial, unfortunately, do not cure patients whose tumors have these mutations, and resistance develops after long time use. We're attempting to enhance the effectiveness of EGFR TKIs by combining TKI therapy with ABT-737, a BCL-2 inhibitor."

According to Gong, mutated EGFRs produce growth signals that drive uncontrolled lung tumor cell division. Inhibition of mutated EGFR is a very effective treatment for these types of lung cancers, she says.

Gong and her colleagues at Memorial Sloan-Kettering demonstrated how lung cancer cell lines with EGFR mutations undergo apoptosis when exposed to erlotinib. In particular, they found that such cells die by a mechanism called the intrinsic apoptotic pathway. Erlotinib, the researchers say, induces dramatic changes in the pro-apoptotic protein, BIM, and this protein is required for erlotinib-triggered cell death.

"The improved understanding of how EGFR mutant cells actually respond to EGFR TKIs will help us to identify strategies to enhance tumor cell death and will also help us to look for possible reasons why tumor cells persist despite treatment," Gong said.

In studies of EGFR TKI-sensitive cancer cells, the researchers found that ABT-737 significantly enhanced erlotinib-induced cell death. "It is proof of principle that you can enhance tumor response to EGFR TKIs by priming tumor cells to a more death-prone state with small molecules that manipulate the intrinsic apoptotic pathway," Gong said. "We hope to design clinical trials based on this strategy, in order to achieve better and longer clinical responses for patients who benefit from EGFR TKIs."

Gong is part of the laboratory of William Pao, M.D., Ph.D. Their studies were funded by the Doris Duke Charitable Foundation and the Labrecque Foundation. ABT-737 is under development by Abbott Laboratories, Inc.

TRAIL-receptor antibodies synergize with chemotherapy to enhance anti-tumor activity in cholangiocarcinoma: Abstract B 50.

A common chemotherapy regimen, when given before either one of two engineered human antibodies, greatly increases the effectiveness of the antibodies against cholangiocarcinoma (CCA), a rare and deadly cancer of the ducts that drain bile from the liver, say researchers from Human Genome Sciences, Inc., a biopharmaceutical research company based in Rockville, Maryland. If their findings in cell culture and animal models of CCA can be applied to humans, the combination of cisplatin, 5-fluorouracil or gemcitabine with a TRAIL-receptor antibody would be the first effective treatment for this disease, they say.

The two antibodies react with different, yet related, cell surface proteins called TRAIL-R1 and TRAIL-R2, which are common to many human cancers. While they are distinct receptors, these two receptors both receive signals that activate biochemical pathways leading to programmed cell death, the researchers say. The TRAIL-R1 antibody (known as mapatumumab) and TRAIL-R2 antibody (lexatumumab) are both being evaluated in clinical trials by Human Genome Sciences.

"Many cancers use the TRAIL pathway as a preferred way to die - a dominant biochemical pathway - and we are in the process of exploring how we can better activate the TRAIL pathways to enhance cell death in the tumor cell," said Robin C. Humphreys, Ph.D., associate director in the Oncology Research Department at Human Genome Sciences. "When we pre-treat CCA cell lines with conventional chemotherapies, the drugs seem to increase the cytotoxicity of the TRAIL-receptor antibodies, as if conventional chemotherapy can lower the cell death threshold of cancer cells enough for the TRAIL pathway to be more effective."

Humphreys and his colleagues experimented with combinations of cisplatin, 5-fluorouracil and gemcitabine given with or prior to treatment with the human TRAIL-receptor antibodies in cholangiocarcinoma cell cultures. Their findings indicated that treating CCA cell lines with a single chemotherapeutic agent 24 hours before administering either antibody increased cytotoxicity, killing nearly 90 percent of cells. According to Humphreys, mouse xenograft studies showed that co- or pre-treatment of a CCA xenograft tumor with cisplatin or gemcitabine before administering mapatumumab significantly inhibited tumor growth and displayed tumor regression over the 40-day period of the trials.

Since human biliary cancer remains a relatively rare cancer, with an annual incidence of about one or two cases per 100,000 people in the Western world, there has been little research toward a specific treatment for this disease, the researchers contend. This pre-clinical data supports potential clinical trials of a TRAIL-R mAb and chemotherapy combination in CCA, Humphreys says.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In San Francisco (10-22-10/16):
415-348-4521

Advances in Drug Screening: Building a Better Haystack for the Needles of Tomorrow

registration@aacr.org () — Tue, 23 Oct 2007 12:00:00 GMT

SAN FRANCISCO - With the discovery of suitable molecular targets - cellular molecules along pathways crucial for sustaining the life of cancer cells - comes the perplexing dilemma of where to find the next therapeutics that will bind to and disable those targets. While the possibilities for drug designs are near-limitless, the methods to screen drug databases and repositories are often problematic or ill-suited for the particular needs of researchers.

Today at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, researchers report new means of delving into vast stores of data in search of potential therapies, whether to find the next natural cancer fighter or to discover new classes of therapeutics.

Targeting neuroblastoma tumor-initiating cells: High-throughput screening strategies to identify novel chemotherapeutics: Abstract A 205.

While research has yielded exceptional advances in treatment and therapeutics for most adult cancers, there has been little improvement in survival rates for patients with the deadly childhood cancer neuroblastoma for the past 30 years. Armed with advances in stem cell knowledge, researchers at The Hospital for Sick Children in Toronto, Canada, are screening currently approved drugs for new neuroblastoma therapies that kill cancer while sparing children exposure to excessive amounts of toxic therapeutics.

Using their screening process, the researchers searched more than 5,000 drugs and uncovered 47 candidates that show good potential against neuroblastoma, including rapamycin, on which the researchers are currently focusing.

"Neuroblastoma is particularly difficult to treat without aggressive chemotherapy and, even when treated successfully, the chemotherapies currently in use frequently have side effects that can have devastating repercussions later in life," said Kristen Smith, Ph.D., a postdoctoral fellow at The Hospital for Sick Children. "We have developed an efficient screening process based on stem cells present in the growing bodies of children, cells that might be susceptible to harm from the necessary blunt force use of therapeutics."

Smith and her colleagues used a cell-based assay program that pits chemotherapeutics against neuroblastoma tumor-initiating cells (TICs) and skin-derived precursors (SKPs). As their full-name suggests, TICs are cancer stem cells developed from tumor samples removed from children. SKPs, however, are normal non-cancerous stem cells found in the skin. Both varieties of stem cells originate from the neural crest, the portion of a developing embryo that eventually comprises the peripheral nervous system.

"The idea is to find a drug that can kill a neuroblastoma TIC without harming an SKP," Smith said. "We reasoned that if the drug is potent enough to kill a tumor stem cell - without damaging a normal stem cell - then we may lessen the risk of SKPs or other stem cells becoming cancerous later in life."

According to Smith, 40 of the 47 drugs that were recognized in the screening have never been used to treat neuroblastoma. The researchers are currently studying the highlighted drugs in TICs from multiple neuroblastoma patients. One drug in particular, rapamycin, has already been studied in an animal model of neuroblastoma, with promising results and is in clinical studies, Smith says.

The work was performed in collaboration with clinicians at The Hospital for Sick Children, Alessandro Datti, Ph.D., at the Mt. Sinai Robotics Facility, and Herman Yeger, Ph.D. and Sylvain Baruchel, M.D. at the Hospital for Sick Children.

The research was funded by the National Cancer Institute of Canada, Canadian Stem Cell Network, McLaughlin Centre for Molecular Medicine, The James Birrell and Lilah Funds for Neuroblastoma Research, and the Sick Kids Foundation.

Identification of inhibitors for MDM2 ubiquitin ligase activity from natural products by a novel high throughput electrochemiluminescent screen: Abstract C 55.

Scientists laboring intensively to develop new therapeutics often turn to naturally produced molecules used by plants or microrganisms to ward off predators. The effectiveness of natural products such as Taxol (derived from tree bark) or rapamycin (derived from soil bacteria) prompted the National Cancer Institute (NCI)'s Natural Products Repository to collect and store over 220,000 biodiverse samples, derived from marine organisms, microbes, and plant life gathered from locations across the globe.

Researchers at NCI's Center for Cancer Research (CCR) report their successful use of a new technology capable of mass-screening extracts from natural products for new potential therapies. In an initial run of the high-throughput screen, the Repository team uncovered a plant compound that blocks the breakdown of the well known tumor suppressor protein called p53.

"The samples in the Repository exist as extracts from specimens that have been collected in the oceans and forests of the world and shipped here - each containing thousands of compounds," said Barry O'Keefe, Ph.D., a researcher at NCI's campus in Frederick, Maryland.

"Somewhere among these samples are natural molecules that have been honed by nature that could have great therapeutic value, but finding them amid the clutter of other natural compounds is difficult."

Their latest natural products screen uses an "electrochemiluminescent" assay, developed by CCR researcher Allan Weissman, M.D., which tags the target proteins and causes them to emit photons, or "light up" when an electrical current is passed through them. If the activity of the target protein is blocked (a sign that some molecule is "inhibiting" the target), the reaction goes dark.

To verify that the electrochemiluminescent assay worked properly, the Repository team searched for a molecule that inhibits the known ability of MDM2 to signal for the destruction of the pro-apoptosis (cell suicide) protein p53. In normal cells, MDM2 and p53 exist in a state of benign equilibrium - balanced to assure that cell suicide does not occur.

The researchers screened over 144,000 samples and uncovered almost 2,000 potential "hits" against MDM2. These hits were further refined, yielding 372 extracts from which chemists are now isolating active compounds. Among the active compounds recovered, one plant chemical called sempervirine was found to induce apoptosis in cancer cell lines.

"Searching through the literature we discovered that sempervirine had been previously considered by French cancer researchers in the 1980s, but since the roles of p53 and MDM2 were poorly understood at the time, sempervirine research took a different direction," O'Keefe said. "Now we will take another look at this compound while we continue to analyze the other extracts."

Identification of equal MDMX/MDM2-p53 interaction small molecule inhibitors: Abstract A 208.

Half of all cancers occur because of a mutation in the tumor suppressor gene p53, while in numerous other cancers its protein is deregulated, taken out of service before it can do its job as a potent anti-cancer regulator. Now, researchers at St. Jude Children's Research Hospital in Memphis, Tennessee have developed a strategy for stopping two key regulators of p53 that can contribute to cancer progression: proteins called MDMX and MDM2. Using biochemical assays developed at St. Jude, the researchers report the discovery of two small inhibitor molecules that can keep both MDMX and MDM2 from deregulating p53.

"We now have an understanding of how MDMX and MDM2 target functional p53, but the real challenge has been to find a means of controlling both MDMX and MDM2," said Damon Reed, M.D., a researcher at St. Jude Children's Research Hospital. "We are looking for a single therapeutic that will knock out both proteins, thereby allowing p53 to do its job, that is, to kill cancerous cells."

While Reed and his colleagues have developed their process to look for new therapeutics for retinoblastoma, a rare childhood cancer of the eye, they believe small molecule inhibitors they have developed will have a much broader impact. "There are a number of cancers in which there is nothing wrong with p53, but the genes for MDM2 and MDMX are over-expressed, such as instances of retinoblastoma, leukemia, breast, lung, prostate, and colon cancers," Reed said. Through funding from the National Cancer Institute, Reed adapted two biochemical assays, fine tuning them to test over 6,000 biologically active compounds for those that could, ideally, bind to both MDM2 and MDMX. In the first test, fluorescence polarization, the researchers linked fluorescent tracers - molecules with the property to rotate light - to a p53-like molecule. If a candidate molecule binds to the MDMX protein it prevents the p53 binding, and, therefore, changes the signal of the fluorescent light.

The second assay, an AlphaScreen test, involves attaching small beads to both the p53-like molecule and either MDM2 or MDMX. If the tested compound binds to MDMX or MDM2, it blocks a chain between the two beads, which decreases the amount of light emitted by the beads.

The St. Jude researchers ran the 6,000 compounds through both the AlphaScreen and the fluorescence polarization assay and discovered two small molecules which bound MDMX and MDM2. According to Reed, the St. Jude team is continuing testing on the two identified molecules in cell culture, and is preparing the molecules for further testing in animal models.
In addition, the St. Jude team has expanded its search for novel, high affinity MDMX/MDM2 inhibitors using a 350,000 compound chemical library.

Targeted approach towards inhibition of telomere-hnRNP A1 interaction: Abstract A 207.

Immortality is a term often used to describe the sustained longevity of cancer cells, which allows them to grow out of control and spread. The lifespan of a cell is determined by portions of DNA called telomeres, which stabilize the cap-ends of the chromosome structures of cellular DNA. Researchers at Gemin X Pharmaceuticals, Inc. in Montreal, Canada, report the development of a combined computer/laboratory system to address the labor-intensive task of screening millions of molecular compounds for the ability to disrupt telomere maintenance. Through their screening process, the researchers have identified two molecules that serve as potent inhibitors of A1 and A2, proteins that sustain telomeres and thus the immortality of cancer cells.

Like the plastic aglets at the ends of shoe strings, telomeres are regions of the chromosome that keep the DNA from fraying at the ends. The telomere consists of a short repeated segment of six DNA nucleotide subunits -thymine, guanine and adenine - in the order of TTAGGG. Gradually, telomeres erode, a trait that has evolved to enforce a cell's mortality: a cell can only grow and divide so many times before its DNA becomes too unstable. This instability occurs when telomeres shorten below a critical threshold. In cancers, the telomere structures are maintained but they require capping proteins such as A1 and A2 in order to permit cell immortality.

In many cancers, the genes that encode A1 and A2 are over-expressed, leading to an overabundance of the proteins and, therefore, longer-lasting telomeres.

"We are seeking to halt tumor growth by taking the immortality out of cancer cells. Moreover, by targeting A1 and A2, the immediate response of the cancer cell is cell death," said Richard C. Marcellus, Ph.D., a researcher at Gemin X.

"Since the A1 and A2 proteins bind directly to DNA, we were looking to find a molecule that could block this specific protein/DNA interaction," Marcellus said. "However, the chemistry involved in building small molecules that are able to inhibit protein/DNA binding is daunting, so most drug developers have looked elsewhere for easier targets."

To find these previously unidentified small molecules, the researchers at Gemin X began with the active area found in the A1 and A2 proteins. While they are slightly different molecules, both proteins bind to the same portion of the six nucleotides found in repeated telomere sequences - the central TAG component of TTAGGG - and the researchers used previously published structural data to create a molecular "footprint," the shape needed to bind DNA.

They then created a computer model of this footprint, which they could use to screen through commercially available databases of small molecules without an exhaustive laboratory assay.

"We acquired as many molecular libraries as we could acquire, totaling some two million potential candidates," Marcellus said. "It was an initial, brute force approach that we could use to quickly discard candidates that wouldn't work."

The initial screen winnowed the field of potential A1 and A2 inhibitors down to two thousand candidates, enabling researchers to move from the in silico approach to the more traditional "wet lab." The researchers then ran the remaining candidates through a gamut of six separate assays, each designed to further weed out inappropriate molecules. The testing included determining whether the molecule actually bound to A1, a solubility assay to discard molecules that stuck to other molecules without specificity, binding studies to determine if the molecule stuck to DNA, binding studies to determine if the molecule stuck to unrelated proteins and an assessment of the molecule's ability to bind to TAG.

Any molecules that made it through those assays were met with one final test: cytotoxicity - could the candidate, in fact, kill cancer cells? The researchers uncovered five classes of compounds that could halt growth and induce death in skin and lymphoma cancer cells. From those five, Marcellus said, they have identified two classes that would be suitable candidates for further refinement, a necessary step before testing in animal models.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In San Francisco (10-22-10/16):
415-348-4521

Clinical Studies in the Pipeline: The Therapies of Tomorrow in Trials Today

registration@aacr.org () — Tue, 23 Oct 2007 12:00:00 GMT

SAN FRANCISCO - Studies presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics demonstrate the flexibility of targeted therapy techniques, where new drugs can be developed and tested in human trials more quickly and safely than ever before.

Among the studies presented include a pair of reports on two separate novel insulin-like growth factor receptor enzyme inhibitors, both currently involved in solid tumor clinical trials. In addition, researchers will be offering details on two Phase II trials involving already-approved drugs in new applications: sunitinib in a form of liver cancer and sorafenib, combined with the cell-signaling molecule IL-21, in metastatic renal cancer.

Efficacy, safety, and changes in angiogenic markers following sunitinib monotherapy in patients with advanced hepatocellular carcinoma: Experience from a phase II study: Abstract PR 7.

Use of sunitinib, designed to reduce tumor angiogenesis, appears to offer early evidence of antitumor activity for patients with a difficult to treat liver cancer known as advanced hepatocellular carcinoma (HCC), say researchers at Dana Farber Harvard Cancer Center.

Results from a 30-patient Phase II study in HCC of the agent, which is approved for use in kidney and rare stomach cancers, show that cancer stabilized in 10 patients for at least three months while one patient had a partial response. Overall, the agent offered a progression-free survival of four months, says the study's lead investigator, Andrew X. Zhu, M.D., Ph.D., an attending oncologist at Massachusetts General Hospital Cancer Center and an assistant professor of medicine at Harvard Medical School.

"We have seen preliminary evidence of anti-tumor activity, and although it is modest, it is also encouraging because all of these patients have cancer that cannot be removed by surgery or which has metastasized," Dr. Zhu said. "This is a small, single arm study so there is need for more research to confirm this potential benefit, and to examine safety more closely." The treatment was generally well tolerated in most patients, Dr. Zhu says, but adds that grade three and four toxicities were observed in approximately three to 20 percent of patients, depending on the specific side effect.

HCC is most commonly found in patients with chronic viral hepatitis (B or C) or with cirrhosis, and surgery to remove tumors is only possible in a small percentage of patients. Generally, patients have a poor prognosis because these tumors produce a lot of proteins, such as VEGF and VEGFR2, that make them highly vascular and able to build a solid and nurturing blood supply with increased ability to invade surrounding major vessels and to metastasize, Dr. Zhu says. Sunitinib is a receptor tyrosine kinase inhibitor designed to target and block VEGFR2 activity, among other pro-growth molecules.

To find out if sunitinib could target HCC, the research team employed a number of research tools to measure changes in the patients' blood and tumor perfusion. "Instead of just trying to determine if the drug is attacking the tumor, we want to get a sense of what kind of changes the agent might be inducing," Dr. Zhu said. "We want to know what the mechanisms are that might confer benefit as well as toxicity."

The team used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess changes in the permeability of tumor blood vessels and found that it decreased by an average of 38 percent after two weeks of sunitinib therapy. Using protein arrays to test for angiogenic biomarkers in the blood, the investigators found that the levels of VEGF and PIGF increased, while that of soluble VEGFR2 declined in most patients. Also, flow cytometry analyses of blood cells suggested that circulating endothelial cells increased in some patients while circulating progenitor cells were significantly decreased, indicating that sunitinib may indeed target key angiogenesis pathways in relevant cell populations.

"These are very interesting changes in blood markers induced by sunitinib. Ongoing studies of these and of other markers might help us to understand how the drug works in HCC and what changes might be relevant in predicting the potential clinical benefits in these patients," Dr. Zhu said.

The Harvard Medical School research team involved in this study includes Dushyant Sahani, M.D., and Rakesh K. Jain, Ph.D. The study was funded by Pfizer, Inc., manufacturers of sunitinib (marketed as Sutent).

Recombinant IL-21 in combination with sorafenib: Preliminary results from a phase I/II study in patients with metastatic renal cell cancer: Abstract A 60.

Two drugs appear to work better than one in treatment of patients with metastatic kidney cancer, according to early results from the first and only clinical trial testing a combination of sorafenib and recombinant interleukin-21.

Among 11 patients with renal cell carcinoma who have gone on to have two or more rounds of combination treatment, 10 have experienced tumor shrinkage, and four patients have had 30 percent or greater reduction in tumor size as measured by the investigators. A total of 13 patients have been enrolled so far in this Phase I study, which is testing three different dose levels.

"These preliminary data are encouraging, as treatment with sorafenib alone was associated with a confirmed overall response rate of only two percent in the Phase III trial that led to regulatory approval," said the study's lead investigator, John A. Thompson, M.D., a professor of medicine at the University of Washington and a member of the Fred Hutchinson Cancer Research Center. The study was funded by Zymogenetics, which developed recombinant interleukin-21 (IL-21).

"However, at this point the number of patients treated in our study is still small and it is too early to draw a definite conclusion concerning the efficacy of interleukin-21 in combination with sorafenib compared to use of sorafenib alone," he said. To date, most adverse events seen have been mild and moderate, Dr. Thompson adds.

Because the two drugs work in very different ways and both have low toxicity profiles, the researchers predicted they would have additive or even synergistic effects when used in combination. Pre-clinical studies in mice showed that, indeed, the two together work better than either alone, Dr. Thompson says.

Sorafenib, a tyrosine kinase inhibitor approved for use in December 2005 under the trademark Nexavar, blocks enzymes in cancer cells that promote tumor growth and also blocks blood vessel growth in tumors, thereby depriving the tumor of nutrients and oxygen. "Although sorafenib does not typically cause a large shrinkage of the tumor, it can prevent the tumor from growing further, and has been shown to delay the progression, or growth, of kidney cancer," Dr. Thompson said.

Recombinant IL-21 activates the immune system to kill cancer cells. "Immune therapies have been shown to work in kidney cancer in the past, but those previously available were very toxic and poorly tolerated by most patients. Recombinant IL-21 is well tolerated by most patients," Dr. Thompson said. "In our clinical trial of recombinant IL-21 by itself, we saw encouraging responses in patients with kidney cancer."

Therefore, treatment with sorafenib may make the cancer more susceptible to a killing response by an activated immune system, he says. "We are looking forward to the Phase II portion of the study to better evaluate the overall safety profile and anti-tumor activity," Dr. Thompson said.

Preclinical characterization of OSI-906: A novel IGF-1R kinase inhibitor in clinical trials: Abstract: C192

Preclinical studies suggest that a small molecule inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) may be an effective anticancer drug in patients, and may have even more benefit when combined with the drug erlotinib (Tarceva), say researchers from OSI Pharmaceuticals, Inc.

OSI-906 is the first small molecule that selectively targets the IGF-1R receptor to enter Phase I trials - two multi-center dose escalation studies of patients with advanced solid tumors. The researchers offer their first presentation of the agent's structure and preclinical pharmacology at the 2007 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting.

The insulin-like growth factor receptor (IGF-1R) is an enzyme expressed on the surface of many human cancer cells, and is known to be a driver of tumor growth. OSI-906 blocks IGF-1R activation of the key cancer cell signaling pathways AKT and MAP kinase, researchers say. In laboratory studies of 28 human tumor cell lines, OSI-906 reduced growth of 15 cell lines representative of colorectal, lung, breast, pancreatic, and pediatric tumors and in mouse models. OSI-906 was particularly effective against tumors that are highly IGF-dependent such as colorectal cancers. According to the researchers, OSI-906 not only slowed tumor growth in mice, but decreased the size of some pre-existing tumors.

"Blocking IGF-1R may not always be enough because cancer cells can use other receptors to grow, especially the epidermal growth factor receptor (EGFR) which is known to be activated in many human cancers," said Jonathan Pachter, Ph.D., senior director of Cancer Biology at OSI Pharmaceuticals, Inc. "Therefore, we hypothesized that the combination of OSI-906 to block IGF-1R together with the anticancer drug Tarceva, which blocks EGFR, would lead to even more effective reduction of cancer growth in cellular and animal models."

In mice with human colorectal cancer tumors, oral administration of OSI-906 or erlotinib alone significantly reduced further growth of the tumors. But when the two drugs were combined, tumor growth was fully halted, and the tumors decreased in size by 22 percent, the researchers say.

OSI Pharmaceuticals, which also developed Tarceva, discovered OSI-906 in its research laboratory in Long Island, N.Y.

A phase I study of R1507, a human monoclonal antibody IGF-1R (insulin-like growth factor receptor) antagonist given weekly in patients with advanced solid tumors: Abstract A 78.

Targeting the receptor for insulin-like growth factor 1 has been a recent trend in cancer drug development. IGF-1 is one of most potent natural activators of the AKT and MAPK signaling pathways which promote cell growth and cell survival. Now, one of the first anti-IGF-1R agents to be tested in a Phase I clinical trial shows the drug to be safe, with few serious side effects and with early evidence of promising benefit in patients with sarcomas.

In a Phase I clinical trial of R1507, a human monoclonal antibody, administered weekly by intravenous infusion, nine of 34 adult patients with advanced solid tumors experienced a period of stable disease, and the seven heavily pretreated patients who remain on study all have sarcomas and show shrinkage or continued lack of growth of their tumors. Four of these patients have Ewing's sarcoma, a rare cancer usually found in children or young adults. These results have led to follow-up studies testing the agent in both pediatric patients and in adults with sarcoma. This study is sponsored by Roche.

"For these patients to have control of their disease implies significant activity, but because the number of patients studied is so small, it is impossible to draw significant statistical conclusions," says one of the study's lead investigators, Stephen Leong, M.D., assistant professor of medical oncology at the University of Colorado Cancer Center.

"This drug and others like it that attack the IGF pathway may provide a new class of drugs to treat a variety of cancers, including breast, prostate, colon, melanoma, myeloma and a variety of sarcomas, which could greatly add to the way that we currently treat these patients," said Dr. Leong.

The researchers found that once a week administration of R1507 was well tolerated with very few side effects and none of those typically associated with cancer therapy, such as low blood counts, risk for infection, hair loss, severe nausea and vomiting. Although the vast majority of side effects were mild - lower than what the researchers classified as grade 3 intensity - there were two serious adverse events (stroke and high bilirubin, a breakdown in red blood cells) in patients while they were on treatment. But it is not certain that the adverse events were caused by the drug, Dr. Leong says. "With a very small number of patients treated, the true and related side effects are still being evaluated," he said.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In San Francisco (10-22-10/16):
415-348-4521

New Cancer Targets, New Therapeutics and Clinical Trials Among Subjects of AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

registration@aacr.org () — Tue, 16 Oct 2007 12:00:00 GMT

San Francisco, October 22-26, 2007

PHILADELPHIA - Merging technological innovations and new knowledge about basic cancer biology, cancer researchers now target specific molecules involved in critical chemical pathways of cancerous cells. The approach opens the door to more effective drug therapies and treatment strategies, advances that will be the focus of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics - the premier international meeting featuring novel cancer therapeutics - to be held October 22 to 26 at the Moscone West Convention Center, San Francisco, California.

Each year, the American Association for Cancer Research (AACR), jointly with the National Cancer Institute (NCI) and the European Organisation for Research and Treatment of Cancer (EORTC), brings together scientists and other professionals from around the world seeking to share the latest information in this field, otherwise known as molecular targets of cancer.

"We are in the midst of a remarkable period of exploration and experimentation in cancer research, with tools and technologies in place to put into practice what might only have been theory just a few short years ago," said Sara A. Courtneidge, Ph.D., a co-chairperson on the Scientific Committee for the meeting and professor at The Burnham Institute for Medical Research in La Jolla, California. "This meeting - where researchers can talk face-to-face about the latest information and reports from continuing studies - is a necessary part of the process of scientific discovery."

More than 3,000 scientists and clinicians - from the laboratories of universities, medical centers and pharmaceutical companies worldwide - are gathering in San Francisco to present and discuss novel cancer research findings. The AACR has selected 24 scientific abstracts for presentation by their authors in five press briefings, each highlighting a critical or emerging area of molecular target research, such as:

The promising results of a Phase I trial of a novel antibody against the insulin-like growth factor receptor in patients with advanced solid tumors have prompted researchers based at the University of Colorado Health Sciences Center to initiate a Phase II trial.

Screening the NCI's vast Natural Products Repository for the next Taxol is a complicated task with innumerable rewards. The National Cancer Institute maintains the world's largest database of natural compounds, representing biologically diverse organisms from across the globe. However, screening these unpurified samples involves complicated chemistry. NCI researchers have used advanced screening techniques to uncover a way of "throwing a monkey wrench" into a cell process responsible for a great percentage of human cancers.

Combining therapies to deliver a "one-two punch" against cancer is rapidly coming to fruition in cancer research. Combining approved targeted treatments with other existing and emerging therapies may enhance the effects of the individual treatments, alone. Researchers at the University of Manchester have found, for example, that combining radiotherapy with an inhibitor under development can prevent cancer cells from becoming resistant to radiation.

The discovery of new targets for cancer therapeutics, when combined with high-throughput screening techniques, has made it possible for researchers to rapidly develop new drug candidates that might serve as therapies in multiple cancers. Scientists from ARIUS Research have created a novel antibody that effectively "de-cloaks" cancer cells, enabling the immune system to recognize and attack tumors. Likewise, researchers from University College London have identified the first small molecule inhibitors of protein kinase D, a frequently deregulated pathway in many cancers.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org
In San Francisco (10-22-10/16):
415-348-4521

$2.7 Million Awarded for Metastatic Colon Cancer Research

registration@aacr.org () — Thu, 11 Oct 2007 12:00:00 GMT

PHILADELPHIA - Through the generous philanthropic support of the Littlefield 2000 Trust, the American Association for Cancer Research (AACR) is pleased to announce four recipients of the 2007 Jeannik M. Littlefield-AACR Grants for Metastatic Colon Cancer Research, totaling $2.7 million. Now in its second year, this competitive grant program supports the cutting-edge research of top scientists from around the world, working to accelerate the discovery and development of new treatments for metastatic colon cancer.

Colon cancer is the third most common cancer diagnosed in men and women. An estimated 154,000 new cases will be diagnosed this year in the U.S. alone. While colon cancer in its earliest stages is often treatable, the spread, or metastasis of the disease to other parts of the body makes for a more complicated course of treatment and potentially a poorer prognosis. Metastatic colon cancer research will advance our understanding of disease progression, the goal being to develop improved therapeutics and achieve better outcomes for patients.

With individual grants ranging from $500,000 to nearly $1 million, the Littlefield funding is intended to have high impact and foster tangible progress against metastatic colon cancer. Special emphasis is placed on research that holds promise for bringing new therapeutics for metastatic colon cancer to patients within a one- to two-year period.

The 2007 Jeannik M. Littlefield-AACR grantees are: Michael Kahn, Ph.D., University of Southern California, Los Angeles (USC); Michael Karin, Ph.D., University of California, San Diego (UCSD); Louis Weiner, M.D., Fox Chase Cancer Center, Philadelphia; and Makoto Mark Taketo, M.D., Ph.D., Kyoto University, Kyoto, Japan.

"More than 80 grant applications were submitted and rigorously reviewed by a committee of esteemed senior scientists. Four outstanding projects emerged as the most promising in terms of their potential to make substantive contributions to metastatic colon cancer research and treatment in the near future," said Margaret Foti, Ph.D., M.D. (h.c.), AACR's chief executive officer. "We offer our congratulations to all four investigators and wish them continued success in accomplishing their very relevant and demanding research goals."

Kahn, in concert with his lab at USC, will apply his AACR-Littlefield grant to research and development of a new therapeutic agent that targets and weakens the β-catenin signaling pathway present in colon cancers. Currently, no treatment exists that is specifically aimed at reducing the functions of this pathway, and Kahn and his associates are dedicated to advancing this chemotherapeutic solution through clinical trials for metastatic colon cancer.

Expanding the knowledge and understanding of the connection between inflammation and metastasis of colon cancer will be the focus of Karin and his team of researchers at UCSD. The AACR-Littlefield grant will support Karin's work to explore the effects of different types of inflammation on the spread of colon cancer and potentially inhibit the growth of metastases through the development of new anti-inflammatory therapeutic strategies. Karin is hopeful that his discoveries can lead to new ways of treating metastatic colon cancer, using both new and existing anticancer therapies.

Weiner and his team at Fox Chase Cancer Center will allocate AACR-Littlefield grant support for unprecedented research looking for functional approaches to identifying important drug response-modifying genes that can be therapeutically targeted to improve colorectal cancer treatment. Weiner's research seeks an analytical and experimental basis for introducing new ways of treating colorectal cancers with existing agents, specifically EGFR pathway-targeted drugs. He expects that these findings can act as a vast resource for future research studies of this type.

Taketo of Kyoto University will apply his AACR-Littlefield grant to support his team's research aimed at inhibiting the CCR1 protein as a way to contain and minimize the invasion and spread of colon cancer throughout the body. Taketo plans to use a cellular targeted therapy approach, as opposed to molecular targeted therapy, with the hope of reducing the side effects of treatment and developing a new approach to treating metastatic colon cancer.

The Jeannik M. Littlefield-AACR Grants for Metastatic Colon Cancer Research are sponsored by Jacques and Sandy Littlefield of Portola Valley, CA, on behalf of the Littlefield 2000 Trust. The grants are named in honor of Mr. Littlefield's mother and represent an integral part of AACR's overall grant program for all types of cancer.

To learn more about the Jeannik M. Littlefield-AACR Grants in Metastatic Colon Cancer Research, please visit our website.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Jennifer Ryan
267-646-0448
jennifer.ryan@aacr.org

AACR, Breast Cancer Research Foundation Award Inaugural Grants in Translational Breast Cancer Research

registration@aacr.org () — Thu, 11 Oct 2007 12:00:00 GMT

PHILADELPHIA - Through the generous support of the Breast Cancer Research Foundation (BCRF), the American Association for Cancer Research (AACR) is pleased to announce the inaugural recipients of the 2007 BCRF-AACR Grants in Translational Breast Cancer Research. These grants provide direct support for innovative breast cancer research projects designed to accelerate the discovery, development, and application of new ways to treat breast cancer, or for preclinical research with direct therapeutic implications.

After careful evaluation and assessment by an esteemed scientific review committee, three researchers emerged as the winners of the 2007 BCRF-AACR Grants in Translational Breast Cancer Research. They are: Ingrid A. Mayer, M.D., Assistant Professor of Medicine, Vanderbilt University Medical Center; Alana Welm, Ph.D., Assistant Professor of Oncological Sciences at the Huntsman Cancer Institute, University of Utah; and Douglas Yee, M.D., Cancer Center Director and Professor, University of Minnesota-Twin Cities.

"The AACR congratulates Drs. Mayer, Welm and Yee on this outstanding achievement and applauds their efforts to translate their innovative research into potential treatments for breast cancer," said Margaret Foti, Ph.D., M.D. (h.c.), AACR's chief executive officer. "We are deeply grateful to the Breast Cancer Research Foundation for its commitment to cutting-edge breast cancer research and look forward to a long-lasting partnership in supporting novel translational research."

Currently, an estimated 2 million Americans are living with or have been treated for breast cancer. Approximately 178,480 new breast cancer cases will be diagnosed this year, and about 40,460 will die from the disease. Translational research bridges the gap between laboratory research and patient care. The BCRF-AACR grant program has the vitally important goal of bringing scientific discoveries from the laboratory into breast cancer treatment protocols swiftly, safely and effectively.

Fifty-six grant applications were received and resulted in three awards, each for $233,333, to support promising research projects that could lead to individualized therapeutic options for breast cancer treatment in the near future.

Mayer's research project, titled "Combined Endocrine and ErbB Inhibition in ER+/HER2+ Breast Cancers," will address resistance to endocrine therapies. Through a Phase II study, she seeks to learn if the combination of an aromatase inhibitor with an EGFR/HER2 inhibitor will work better in preventing failure of tumors to respond to anti-hormonal treatment. Mayer hopes that her research will reduce mortality in patients with hormone-responsive HER2-positive breast cancer.

Welm's research, "The MSP Pathway as a Therapeutic Target in Aggressive Breast Cancer," will build upon her earlier studies which found that overexpression of the macrophage-stimulating protein (MSP) pathway drives progression of breast cancer. She validated the clinical relevance of this finding through gene expression data gathered from patients with early-stage breast cancer, showing that overexpression of three genes within the MSP pathway served as highly accurate indicators of poor prognosis in patients with early breast cancer. Her current research seeks to translate these findings to the clinic by developing a diagnostic test for overexpression of the MSP pathway as a biomarker for poor prognosis and to carry out preclinical tests of three MSP pathway inhibitors in order to block growth and/or metastasis of breast cancer.

Yee will look at "Gene Expression Profiling to Predict Response to anti-IGF Therapy." This research builds upon his long-term goal of demonstrating that the insulin-like growth factor receptor (IGF1R) is an excellent target for breast cancer therapy. Yee hypothesizes that expression of specific insulin receptor substrate adaptor proteins link IGF1R to identifiable gene signatures and cancer phenotypes. To test this, Yee aims to develop gene expression profiles to predict which cancers are IGF-driven and, ultimately, which patients may best benefit from these inhibitors. His long-term goal is to use these discoveries to make the use of anti-IGF drugs more effective, and to create a better tool for making personalized therapeutic decisions for breast cancer.

Additional funding for the BCRF-AACR Grants in Translational Breast Cancer Research is generously provided by the AACR Centennial Fund, Amgen, Eli Lilly and Company, and Genentech BioOncology. To learn more about the BCRF-AACR Grants in Translational Breast Cancer Research, please visit our website.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Jennifer Ryan
267-646-0558
jennifer.ryan@aacr.org

The Benefits of Motherhood: Fetal Cell "Transplant" Could be a Hidden Link between Childbirth and Reduced Risk of Breast Cancer

registration@aacr.org () — Tue, 02 Oct 2007 12:00:00 GMT

PHILADELPHIA - Some benefits of motherhood are intangible, but one has been validated through biostatistical research: women who bear children have a reduced risk of developing breast cancer. In Seattle, Washington, researchers at the University of Washington and Fred Hutchinson Cancer Research Center believe they have identified a source of this protective effect: fetal cells "transplanted" to the mother before birth.

Their findings are presented in the October 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

The ability of cells from a growing fetus to take up long-term residence within its mother is a phenomenon called fetal microchimerism. According to the researchers, while fetal microchimerism has been implicated as a mechanism of autoimmune disease, it may also benefit mothers by putting the immune system on alert for malignant cells to destroy.

To test the idea, the researchers recruited 82 women, 35 of whom had been diagnosed with breast cancer. Approximately two-thirds of the women studied have had children, and more than half of the participants had given birth to at least one son. The researchers took blood samples from each participant and searched them for male DNA, as they reasoned it is a relatively definitive matter to detect the male Y chromosome amid the mother's native - and obviously female - cells within a blood sample.

Among the women with breast cancer, only five had male DNA in their bloodstream. Three of the five previously gave birth to sons, one had had an abortion and the other had never been knowingly pregnant. In total, about 14 percent of all women in the breast cancer group had male DNA in their bloodstream compared to 43 percent of women in the non-breast cancer group.

"Our research found that these persisting fetal cells may be giving a woman an edge against developing breast cancer," said lead author Vijayakrishna K. Gadi, M.D., Ph.D., assistant professor at the University of Washington and research associate at the Fred Hutchinson Cancer Research Center. "This experiment of nature is all the more fascinating because for years doctors treated a number of different cancers by transplanting cells from one person to another."

According to Dr. Gadi, these findings could provide a starting point for future research on the role of fetal microchimerism in the prevention of cancer. In addition, there are other reasons for male DNA to be in a woman's peripheral blood, such as miscarriage and abortion - or possibly even blood transfusion or a male twin that was reabsorbed into the womb at an early stage of the pregnancy.

Funding for this study was provided by the National Institutes of Health and Amgen, Inc. Breast cancer patients were recruited through a breast cancer specialty clinic at the Seattle Cancer Care Alliance, which is affiliated with both the Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org

Dietary Calcium Could Possibly Prevent the Spread of Breast Cancer to Bone

registration@aacr.org () — Tue, 02 Oct 2007 12:00:00 GMT

PHILADELPHIA - A strong skeleton is less likely to be penetrated by metastasizing cancer cells, so a fortified glass of milk might be the way to block cancer's spread, according to researchers at the ANZAC Research Institute in Concord, Australia. Using a mouse model of breast cancer metastasis, the researchers found that a calcium deficiency may increase the tendency of advanced breast cancer to target bone. Dietary calcium, they reason, might help prevent the spread of breast cancer to bone and serve as an adjuvant treatment during therapy.

Their findings are presented in the Oct. 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

According to the researchers, about 70 percent of patients who develop advanced breast cancer will have secondary tumors in the bone. The spread of cancer to bones leads to cellular processes that physically break down existing bone, leading to further pain and illness. In fact, the breakdown of bone and subsequent bone re-growth forms what senior author Colin R. Dunstan, Ph.D., terms a "vicious cycle" that turns bone into an environment conducive to cancer growth.

To better understand the role of bone turnover in the spread of cancer, Dunstan and his team compared the effects of a low- and high-calcium diet in mice. They found that dietary calcium deficiency - independent of the chemical factors that control turnover - was related to a significantly higher increase in cancer cell proliferation and the total proportion of bone that had been penetrated.

"These results could have implications for patients with breast cancer bone metastases or who are at high risk for developing metastatic disease," Dunstan said. "Many older women in our community are known to be calcium deficient due to low calcium dietary intake or due to vitamin D deficiency. These women could be at increased risk for the devastating effects of bone metastases."

According to Dunstan, his results call for further, directed clinical trials "to investigate how calcium and vitamin D status influence progression to metastatic disease, and to determine if corrections of calcium and vitamin D deficiencies are important in breast cancer patients."

The ANZAC Research Institute study was funded by the National Health and Medical Research Council of Australia and the New South Wales Government.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
greg.lester@aacr.org

To Evade Chemotherapy, Some Cancer Cells Mimic Stem Cells

registration@aacr.org () — Wed, 19 Sep 2007 12:00:00 GMT

ATLANTA - Anti-cancer treatments often effectively shrink the size of tumors, but some might have an opposite effect, actually expanding the small population of cancer stem cells believed to drive the disease, according to findings presented today in Atlanta, Georgia at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

"Our experiments suggest that some treatments could be producing more cancer stem cells that then are capable of metastasizing, because these cells are trying to find a way to survive the therapy," said one of the study's investigators, Vasyl Vasko, M.D. Ph.D., a pathologist at the Uniformed Services University of the Health Sciences in Bethesda, Md.

"This may help explain why the expression of stem cell markers has been associated with resistance to chemotherapy and radiation treatments and poor outcome for patients with cancers including prostate, breast and lung cancers," Dr. Vasko said. "That tells us that understanding how to target these markers and these cells could prove useful in treating these cancers."

The cancer stem cell markers include Nanog and BMI1, both of which contribute to stem cells' defining ability to renew themselves and differentiate into different cell types, Dr. Vasko said. These same molecules are found in embryonic stem cells.

Researchers have recently debated the notion that some therapies are not capable of eradicating cancer because they do not target the cancer stem cells responsible for tumor development. To test this hypothesis, Dr. Vasko, along with scientists from the CRTRC Institute for Drug Development in San Antonio and from the Johns Hopkins University, set out to measure both stem cells markers and tumor volume before and after treatment in a mouse model.

They selected a rare form of cancer, mesenchymal chondrosarcoma (MCS), which has not been well described and for which there is no effective treatment. The researchers first determined that Nanog and BMI1 stem cell markers were more highly expressed in metastatic tumors compared to primary tumors. "This suggests that expression of the marker plays some role in development of metastasis," Dr. Vasko said.

They then applied various therapies - from VEGF inhibitors such as Avastin to the proteasome inhibitor Velcade - in mice implanted with human MSC, and analyzed the effects on tumors. Some of the treatments seemed to work, because they led to a dramatic decrease in the size of the tumors, Dr. Vasko said. But analysis of stem cell expression before and after treatment revealed that even as some anti-cancer treatments shrank tumors, they increased expression of Nanog and BMI1. "These treatments were not enough to completely inhibit tumor growth, and the cancer stem cell markers were still present," Dr. Vasko said.

Use of the agents Velcade and Docetaxel led to the most significant increase in stem cell markers within the treated tumor, while ifosfamide and Avastin inhibited expression of the markers in this cancer subtype.

"We hypothesize that the tumor escapes from chemotherapy by induction of stem cell marker expression," he said. "The small number of cells that survive the treatment could then generate another tumor that metastasizes."

Dr. Vasko doesn't know how this happens, but theorizes that "dying cells could secrete a lot of factors that induce expression of stem cell markers in other cancer cells. I think they are trying to survive and they use a mechanism from their experience of embryonic life."

If scientists understood the pathways cancer stem cells use to survive treatment or increase their ranks, then therapeutic targets could be developed, Dr. Vasko said. Some novel therapies are already being tested against cancer stem cells, he added.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org
In Atlanta (September 17-20):
404-221-6855

Gene Chip Data Improved Therapy in Some Patients with Incurable Cancer

registration@aacr.org () — Wed, 19 Sep 2007 12:00:00 GMT

ATLANTA - Like many oncologists, Eric P. Lester, M.D., was faced with a dilemma: seven patients with advanced, incurable cancer, an arsenal of drugs that may or may not help them, and not enough solid proof about treatment efficacy to guide him. So Dr. Lester devised what he called a "simple-minded experiment" that illustrates the promise of personalized medicine. Using DNA microarray "chips," Dr. Lester analyzed his patients' tumors for expression of genes associated with good response to various anti-cancer drugs, and based his drug treatment plans on the results. Four out of seven patients with advanced cancer enrolled in the extremely limited study had a better outcome than expected.

The finding, presented today in Atlanta, Ga. at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development, shows that "a personalized molecular oncology approach, basing chemotherapy on relative gene expression in tumors, holds promise even at the relatively crude level employed here," said study investigator, Dr. Lester, president of Oncology Care Associates in St. Joseph, Mich.

To obtain and analyze chip data, Dr. Lester worked with Craig Webb, Ph.D., Director of Translational Medicine at the Van Andel Research Institute in Grand Rapids, Mich.

The study is unusual because oncologists don't yet base most of their treatment decisions on gene profiling, especially when it might involve pairing drugs together in a novel combination or using varied doses, Dr. Lester said. "Much of clinical medicine is an educated guess, and this was an attempt to come up with a better approach by using the technology of a gene chip to make multiple, highly educated guesses simultaneously," Dr. Lester said.

Dr. Lester added that one of the seven participating patients died before the gene chip was used to direct therapy.

Many current clinical trials involving gene expression examine effectiveness markers for individual drugs rather than combinations of drugs or different doses of agents used together for the first time. To truly help the most patients, Dr. Lester said, all potentially effective drugs and combinations must be matched up against the unique genetic profile of a patient's tumor, he said.

"Effective cancer treatment depends on understanding the biology driving the cancer, but because each tumor is different, it is very hard to personalize care and do a rigorous scientific experiment at the same time."

In this study, Dr. Lester said he "stayed within the envelope of a reasonable standard of care" in treating his patients. That standard is often based on what insurance companies will typically reimburse for treatment given published studies about the effectiveness of a drug on a certain tumor type, and whether or not the drug is federally approved for that indication. Dr. Lester and Webb surveyed the scientific literature and compiled a list of genes whose expression levels may predict response to a drug given the tumor type.

In some cases, treatment strategies suggested by the chips varied significantly even for the same type of cancer. For example, one patient whose lung cancer had spread to his brain and bones achieved a "near complete response" when treated with two chemotherapy drugs, in addition to Tarceva and Avastin, while another lung cancer patient responded to third-line drugs such as etoposide.

Acknowledging the risk involved with using novel combinations of drugs where no set safety profile exists, Dr. Lester said that "this is constantly done in medicine. People are taking antibiotics at the same time as using heart and cholesterol pills, and blood pressure medication."

"This kind of polypharmacy will become more common in cancer, but at the moment, it is hard to figure out the difference between doses that are effective or that could be toxic," he said.

The best way to get around such issues is to build a database of gene expression data and match them with patient outcomes, he said. "Now when I see new patients I am itching to look at what the genes can tell me," Dr. Lester said. "It is a smarter way to treat cancer."

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org
In Atlanta (September 17-20):
404-221-6855

Lisa Dunlop Joins AACR to Lead Individual Giving Initiative

registration@aacr.org () — Tue, 18 Sep 2007 12:00:00 GMT

PHILADELPHIA -- Lisa R. Dunlop, CFRE, has joined the American Association for Cancer Research (AACR) as Director of Individual and Planned Giving at the AACR Foundation for the Prevention and Cure of Cancer. In this newly created position, Dunlop will oversee the Foundation's fundraising from individual donors via personal solicitation, direct mail and special events.

Most recently, Dunlop was Chief Development Officer at Boys & Girls Clubs of Philadelphia, which, under her leadership, doubled its annual fundraising in less than four years. With an emphasis on donor-centered fundraising practices, Dunlop established a recognition society for donors, strengthened special events to significantly increase sponsorship revenue, and oversaw the marketing and communications functions, including the recently redesigned website and monthly e-newsletter. Her responsibilities also included overseeing grants administration and working closely with many key Board members and several committees regarding fundraising, marketing, planning and Board governance.

"We are delighted to welcome Lisa to the AACR," said Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.). "At a time when cancer research funding is of paramount importance, Lisa's background and substantial experience in fundraising will be invaluable as we work to increase grant funding opportunities for researchers active in innovative cancer science and discovery around the world."

A graduate of the University of Virginia, Dunlop has held development positions at Beaver College; Abington Memorial Hospital Foundation; Albert Einstein Healthcare Network; Evangelical Services for the Aging Foundation; and Boys & Girls Clubs of Philadelphia. Active in fundraising professional associations since 1987, Dunlop served two terms as a board member and officer of the Association of Fundraising Professionals' Greater Philadelphia Chapter, which has more than 700 current members. Dunlop is also a frequent lecturer at professional conferences.

"Donors to the AACR participate personally in preventing and curing cancer through philanthropic giving, which funds research grants to the best scientific teams worldwide," said Dunlop. "Those who support the AACR have confidence that their gifts will result in discoveries that save lives. I look forward to reaching out to new individuals and sharing the story of how they can become involved."

Strengthening individual philanthropy in addition to AACR's traditional corporate and foundation support reflects the association's strategic vision as it commemorates its 100th anniversary this year. Increased funding will enable the AACR to place even greater emphasis on identifying promising new scientific areas in the field; fostering the highest quality cancer research through its programs; ensuring an appropriate cancer research workforce for the future; incorporating all relevant scientific disciplines within AACR membership and its activities; and maximizing cross-disciplinary interaction and communication, all with the goal of reducing the cancer burden around the world.

Dunlop, her husband and daughter reside in Glenside, Pa., Montgomery County.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Media Contact:

Jennifer Ryan
267-646-0558
ryan@aacr.org

Blood Protein Detects Lung Cancer, Even at Earliest Stage

registration@aacr.org () — Tue, 18 Sep 2007 12:00:00 GMT

ATLANTA - Biopharmaceutical researchers have found a protein in blood they say is linked to all stages of lung cancer but which rarely shows up in the blood of people without the disease. Testing for this protein might help physicians decide whether smokers or others at high risk for lung cancer should be referred for lung imaging, say investigators, who presented their findings today in Atlanta, Georgia at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development. A diagnostic blood test to screen high-risk individuals for lung cancer could be both practical to use and cost-effective, say investigators from Panacea Pharmaceuticals, Inc., of Gaithersburg, Md.

"A positive test for this protein marker, followed by CT scanning, may help identify individuals with lung cancer at a stage in which treatment is more effective, possibly even curative," said research scientist Mark Semenuk, who is presenting results of a study testing the specificity and sensitivity of the blood test.

Currently, there are no approved blood tests available to help detect lung cancer, which is expected to be diagnosed in 213,000 people in the U.S. this year, and will be responsible for more than 160,000 deaths, according to the National Cancer Institute. Typically, CT scanning or chest x-rays are performed on people who have developed symptoms of lung cancer, but by the time a patient is symptomatic the disease is often well advanced. These two methods are not often used in early screening for potential lung cancer given such issues as price and whether radiological methods are appropriate for routine screening on a large scale."

The protein targeted in the blood test is Human Aspartyl (Asparaginyl) β-Hydroxylase (HAAH), which Panacea Pharmaceutical researchers say is abnormally expressed on the surface of cancer cells, compared to normal cells, where it resides inside the cell body. HAAH is also found in the serum of individuals with cancer. The protein recognizes cell surface growth factors and modifies them, Semenuk says, pushing the cells into uncontrolled growth. It is likely that increased expression of HAAH is an early step in cancer development, since all stages of lung cancer express roughly the same level of the protein compared to adjacent normal cells.

Thus detection of HAAH in the bloodstream can detect lung cancer before it becomes symptomatic, he says.

Staining of normal versus cancer cells has found that HAAH is expressed in a wide range of carcinomas, including lung cancer, Semenuk reports. In this study, researchers found that 99 percent of 160 patients who represented all stages and various types of lung cancer, had high levels of HAAH protein in their blood, but only nine percent of 93 non-smokers without lung cancer had a positive HAAH blood test.

In a group of 50 smokers not known to have cancer, four patients had levels of HAAH that were higher than the projected "cut-off" line established between cancer development and no disease, Semenuk says. It is not known, however, whether these four people did eventually develop lung cancer, because the samples were provided for study without access to patient records, and further tests may change that cut-off point, he adds.

"These results are very encouraging, because it points to those patients who are most likely to need further testing," Semenuk said. "Elevated levels of HAAH cannot confirm whether a person has lung cancer, but can be used as a routine screening test for recommending further diagnostic evaluation. That is the way most cancer biomarker tests, like the PSA or CEA, are meant to work, and this may be one of the most effective to date."

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org
In Atlanta (September 17-20):
404-221-6855

A New Technology for Cancer Screening Listens for the Signs of Cancer

registration@aacr.org () — Tue, 18 Sep 2007 12:00:00 GMT

ATLANTA - Cancer-sensing devices built as cheaply and efficiently as wristwatches - using many of the same operating principles - could change the way clinicians detect, treat and monitor cancer in patients. Researchers from the Georgia Institute of Technology have created an acoustic sensor that can report the presence of small amounts of mesothelin, a molecule associated with a number of cancers including mesothelioma, as they attach to the sensor's surface.

According to the researchers, the study is a proof of principle, demonstrating a technique that might work for the detection of nearly any biomarker - a collective term for a molecular signal that denotes the presence of disease. They present their findings today in Atlanta, Georgia at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

"It is one thing to be able to identify biomarkers for a disease, but it is another to be able to find them in blood quickly and easily at very low concentrations," said Anthony Dickherber, a graduate student in the School of Electrical and Computer Engineering at Georgia Tech. "We envision that, one day, doctors can use an array of our sensors as a sort of laboratory in their office, where they could use a quick blood sample to detect or monitor the signs of cancer."

ACµRay™ sensor chip developed by Georgia Tech researchers for early detection of cancer

According to Christopher Corso, the other graduate student engaged in the project and an M.D., Ph.D. student, such a device would be a boon to healthcare practice, allowing physicians to screen patients for signs of disease before opting for more expensive or invasive diagnostic techniques. Responding to the growing need for such sensors in both research and clinical practice, Dickherber, Corso and research adviser William D. Hunt, Ph.D., conceived of and developed the ACuRay^TM(pronounced ak´-u-ra) chip, standing for ACoustic micro-arRay - a device that shares more in common with an inexpensive wristwatch than the sort of cutting edge molecule-sorting apparatuses currently used by researchers and clinical laboratory technicians.

The array consists of a series of electrodes deposited on the surface of a thin film of zinc oxide, which allows the device to resonate, or vibrate, at a specific frequency when a current is applied, much like the quartz timing devices used in many clocks and watches.

"The sensor itself is built on a base of silicon, like a computer chip, and could be mass-produced using very well known and inexpensive microelectronic fabrication techniques," Dickherber said.

To turn this array into a sensor, the Georgia Tech researchers coated the zinc oxide surface with mesothelin-specific antibodies generated in the lab of Ira Pastan, M.D., at the National Cancer Institute. These molecules are engineered versions of the antibodies the immune system creates to identify foreign intruders, such as microbial parasites. In this study, the researchers coated the sensor with antibodies for mesothelin, a cell-surface protein that is highly expressed in mesothelioma, ovarian cancer, pancreatic cancer and other malignancies.

When the mesothelin binds to an antibody, the added mass changes the frequency at which the acoustic wave passes between the electrodes on the surface of the device. The device is able to "hear" the pitch change due to nanomolar concentrations of mesothelin (just a few molecules amid billions) binding to antibodies on the chip. The technology has the potential of detecting biomarkers in even lower concentrations than those tested, Dickherber said.

"It is really an elegant engineering solution to a very complicated problem," said Hunt, a professor of electrical and computer at Georgia Tech and lead researcher on the project. "We could, for example, detect a number of different markers for a single disease on a single chip no bigger than the tip of a fountain pen. With refinement, this technology could readily lead to an inexpensive, ubiquitous technology for researchers, physicians and the clinical laboratory."

This research is supported by grants from the U.S. Army Medical Research & Materiel Command Prostate Cancer Research Program, the National Science Foundation, The V Foundation, the National Cancer Institute and the Georgia Cancer Coalition.

Download a hi-res image of the ACµRay^TM sensor chip developed by Georgia Tech researchers for early detection of cancer.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org
In Atlanta (September 17-20):
404-221-6855

Test for Lung Cancer Looks for Discomforting Quiet among Protective Genes

registration@aacr.org () — Tue, 18 Sep 2007 12:00:00 GMT

ATLANTA - When it is quiet - "almost too quiet" - in movies, it is a sign that something is about to go wrong for the good guys. This holds true for the genes that protect against lung cancer, as researchers at the University of Toledo in Toledo, Ohio, have learned. They identified a panel of 15 genes that could serve to predict cancer; if enough of their collective activity becomes quiet - almost too quiet -- it could mean they are being suppressed by other factors in the cell, a step that may lead to cancer.

According to lead researcher, James C. Willey, M.D., a test for these genes, in normal cells sampled via bronchoscopy, could serve as a technique to identify those individuals genetically at risk for lung cancer. In a study of 49 subjects, Dr. Willey and his colleagues were able to correctly identify the individuals with cancer 96 percent of the time. Dr. Willey presents the team's findings today in Atlanta, Georgia at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

"Smoking causes about 90 percent of all lung cancer cases, yet only about 10 to 15 percent of heavy smokers will develop lung cancer," said Dr. Willey, an associate professor of medicine and molecular biology at the University of Toledo's College of Medicine. "We are looking for new techniques that will allow us to pick out the 10 to 15 percent of individuals at highest risk for lung cancer from the enormous pool of current and former smokers."

While advances in screening tools like high resolution coaxial tomography (HRCT) enable increasingly effective early detection of lung cancer, scanning all present or former heavy smokers is problematic and costly when, due to genetic makeup, 85 to 90 percent of them are at low risk despite smoking history, Dr. Willey said. Therefore, Willey believes that a screen to identify the 10 to 15 percent of high risk individuals should increase the accuracy of further HRCT screening. "In America alone, there are more than 40 million present or former heavy smoking individuals," Dr. Willey said.

To determine which genes are active in lung cancer, Dr. Willey and his colleagues look for levels of messenger RNA transcripts -- instructions copied from DNA that direct cells to create specific proteins. Previously, the researchers had published findings demonstrating that genes responsible for protecting lung cells from damage caused by cigarette smoke or environmental toxins are sub-optimally regulated in the normal lung cells of individuals who develop lung cancer. In this study, Dr. Willey and his colleagues put their theories to the clinical test by measuring transcript abundance (TA) of 15 genes that encode protective antioxidant and DNA repair proteins in lung airway cells taken from 25 people with lung cancer and 24 people without the disease.

Their previous research allowed them to determine the threshold levels of TA for each gene - the point at which the amount of mRNA transcripts would indicate a tendency toward cancer. In this study, they used the threshold levels as a basis to assign a value of one or zero to each of the targeted genes for an individual subject, with "zero" indicating normal TA.

If the sum total of a subject's target genes was greater than or equal to seven, the genes could collectively serve as a biomarker for lung cancer, the researchers found. Their results yielded one false negative and seven false positives among the 49 individuals assessed. According to Dr. Willey, they believe that a positive result in a subject without lung cancer may not actually be false positive, but rather could mean that the person is at an increased risk for lung cancer, which might arise later.

These results justify a larger, prospective study to determine whether this biomarker will be useful in predicting risk for lung cancer in current and former smokers. "Overall, the study showed a high degree of accuracy for picking out lung cancer patients," said Dr. Willey.

This study was funded by the National Cancer Institute. University of Toledo graduate students Thomas Blomquist and D'Anna Mullins, and University of Toledo staff Erin Crawford, Younsook Yoon, Jeffrey Hammersley, Dawn-Alita Hernandez, Jamey Ruiz, Mohammed Al-Baghdadi, and Sadik Khuder all contributed to this study.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Content:
Greg Lester
267-646-0554
lester@aacr.org
In Atlanta (September 17-20):
404-221-6855

Gene Profiling Can Single Out the Worst Cases of Multiple Myeloma and Guide Therapy

registration@aacr.org () — Tue, 18 Sep 2007 12:00:00 GMT

ATLANTA - Multiple myeloma patients vary widely in how they respond to treatment, but now researchers at the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences have identified a small subset of genes whose activity could predict high-risk cases and potentially guide therapy in the future.

Researchers followed 532 multiple myeloma patients for seven years after blood stem cell transplant to create a genetic profile to chart the severity of the disease. The team determined that the activity of as few as 17 genes could mean the difference between high or low risk for a poor prognosis. They present their data today at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development, in Atlanta, Ga.

"There are enormous differences between how different people fare with multiple myeloma. While most do very well others have a highly aggressive form of the disease and this is not recognized well with current prognostic variables," said lead researcher John D. Shaughnessy, Jr., Ph.D., a professor of medicine at the Myeloma Institute for Research and Therapy. "If we can categorize a patient's risk early, we can better guide that patient toward therapies that might be more effective for them based on the genetic profile of the disease."

Multiple myeloma is a cancer affecting the blood plasma cells in bone marrow that produce antibodies. Nearly 14,600 new cases of multiple myeloma occur each year in the United States. The disease is most often treated through the use of high dose chemotherapy and peripheral blood-derived stem cell support. While multiple myeloma often responds well to initial treatment, it often becomes drug resistant and patients are prone to relapse.

According to the researchers, survival varies greatly between low-risk and high-risk patients. "At 24 months, about 90 percent of low-risk patients will be alive, whereas about 50 percent of the high-risk patients have succumbed to the disease," said Fenghuang Zhan M.D., Ph.D., of the University of Arkansas for Medical Sciences.

To understand the possible molecular mechanisms driving initiation and progression of multiple myeloma, the researchers launched a large-scale, longitudinal study to categorize the differences in gene expression patterns, that is, which genes are activated and inactivated, in relatively indolent versus aggressive disease.

Using purified tumor cells taken from 532 newly diagnosed patients who went on to receive uniform therapy, the researchers screened over 54,000 genes across the human genome for signs that might relate to multiple myeloma survival estimates. About 13 percent of all the patients they studied exhibited a genetic pattern that fit into the high-risk category, a frequency that rose to 76 percent among relapsed patients.

"The observation of an increase in the gene expression risk score among relapsed patients provides evidence that there are likely to be small subsets of high-risk cells even in patients with low risk disease, and that current therapeutics are sub-optimal in that they kill off the low-risk cells, leaving behind cells that exhibit a high-risk genetic profile," Shaughnessy said. Currently, the researchers have experiments underway to definitively prove this concept.

Initially, the researchers identified 70 genes linked to early cancer-related death, although further analysis narrowed that number to 17. Remarkably, about 30 percent of the genes that predict high risk are found on chromosome 1, enough so that Shaughnessy recognized a trend among the genes, based on where they map on each chromosome in the human genome. The majority of genes that were up-regulated - or over-produced - in high-risk patients mapped to the long arm of chromosome 1, while the majority of genes that were down-regulated - or suppressed - mapped to the short arm of the same chromosome.

"Together these data suggest that defects in chromosome 1 may be directly related to the acquisition of higher risk in patients with multiple myeloma," Shaughnessy said. "Gene expression profiles have now provided us with signposts that help us risk stratify patients and tailor therapies accordingly."

"Importantly, these data may provide researchers with key insights into molecular mechanisms driving disease severity which might be the target of future therapies," Shaughnessy said.

Funding for this research was provided through grants from the National Cancer Institute, The Lebow Fund to Cure Myeloma, and the Nancy and Stephen Grand Foundation and additional philanthropic support to the Myeloma Institute for Research and Therapy.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org
In Atlanta (September 17-20):
404-221-6855

Liver Cancer Marker Could Yield Blood Test for Early Detection

registration@aacr.org () — Tue, 18 Sep 2007 12:00:00 GMT

ATLANTA - In the face of an emerging liver cancer crisis in Asia, researchers at the Chinese University of Hong Kong have developed a test that could help millions. Due to widespread hepatitis B virus (HBV) infection, nearly 10 percent of China's population is at high risk for hepatocellular carcinoma (HCC), a liver cancer with low survival rates if not detected and treated early. Researchers report on a new blood screening technique that could make it possible to detect early-stage liver cancer and predict how well a patient will do following treatment.

They present their data today at the American Association for Cancer Research's Second International Conference on Molecular Diagnostics in Cancer Therapeutic Development, in Atlanta, Georgia.

According to their report, the Chinese team has detected an altered version of RASSF1A, a tumor suppressing gene, in the blood of HCC patients and in 58 percent of HBV-infected test subjects. Healthy subjects showed no signs of the altered gene. They also found that patients treated for HCC with high blood levels of the gene were more likely to have a relapse of the disease.

"A large portion of the population throughout Hong Kong and China are carriers of hepatitis B, so many people are at risk for hepatocellular carcinoma," said K.C. Allen Chan, MBBS a professor at the Chinese University of Hong Kong. "And we hope that this will form the basis of an effective clinical test for early detection of hepatocellular carcinoma."

Hepatocellular carcinoma is one of the deadliest forms of cancer in China and throughout Asia, according to the researchers. In the West, liver cancer is usually a secondary cancer, caused by the spread of tumor cells from elsewhere in the body. In China, however, liver cancer mainly manifests as HCC, a primary cancer, which has been linked to hepatitis B and C infection and cirrhosis. Noticeable symptoms do not usually appear until the cancer has progressed, so it is rarely caught early, when intervention would be most effective, and survival rates are typically low, said Chan.

Currently, ultrasound and CT scans are the gold standard for detecting HCC. However, they are too expensive to be an effective mass screening tool, the researchers said. About 70 percent of patients exhibit a detectable increase in bloodstream amounts of alphafetoprotein, but a screen for this protein would miss many potential patients. "We need a new biomarker for hepatocellular carcinoma, something that can be used to screen large populations of at-risk people for follow-up studies," Chan said.

RASSF1A is a good candidate, according to Chan. Researchers have known that the DNA of HCC tumor cells lack a functioning copy of RASSF1A. In these cells, RASSF1A is "hypermethylated," meaning the RASSF1A gene has been physically altered by cancer-related processes that added clusters of carbon and hydrogen atoms, called methyl groups, to portions of the DNA within the gene. Hypermethylation is epigenetic - the gene is altered by environmental circumstances and is not inherited. Since the cell's protein making system can't access the gene, hypermethylation effectively knocks out the tumor-suppressing RASSF1A gene, which is then unable to stop cells from becoming cancerous.

While hypermethylated RASSF1A would make a useful biomarker for HCC, methylation-specific PCR - the polymerase chain reaction used to specifically amplify and detect methylated DNA - destroys about 85 to 93 percent of the DNA in a blood sample. Together with the fact that tumoral DNA is only present at very low concentrations in blood during early stages of HCC, this method has not been sensitive enough to detected altered RASSF1A in blood for the purpose of early cancer detection, Chan said.

To compensate, Chan and his colleagues invented a new technique that they call "methylation-sensitive enzyme-mediated real-time PCR," which combines real-time PCR, a technique that enables researchers to simultaneously detect and amplify a given gene, with an enzyme that breaks unmethylated DNA apart. With this new technique, Chan's team was able to separate out the altered methylated DNA, thus developing a more sensitive technique for detecting and quantifying hypermethylated RASSF1A derived from cancer cells in blood.

To test the relationship between altered RASSF1A and HCC - as well as test the new detection technique -- Chan and his colleagues conducted two studies involving HCC patients. In the first, they matched 63 pairs of patients, one with HCC and the other a chronic HBV carrier by age and sex, along with 30 healthy volunteers. They detected hypermethylated RASSF1A in 93 percent of the HCC patients, 58 percent of the HBV carriers and none of the healthy patients. The median RASSF1A levels for the HCC patients were 770 copies per milliliter and 118 copies per milliliter for HBV carriers.

"The respective levels of the gene for HCC patients and HBV carriers, is consistent with what we already know about the progression of the disease," Chan said. "The gene is altered very early in the procession of malignant transformation, and so we can see that the levels of the altered gene increase as the cancer process progresses."

In the second study, the researchers looked at 22 pairs of sex- and age-matched patients who had been enrolled in a HCC surveillance program involving 1018 HBV carriers. For the 22 HBV carriers who subsequently developed HCC, there was a significant increase in circulating RASSF1A levels from the time of enrollment to the time of cancer diagnosis. On the contrary, there was no significant change in RASSF1A levels over the same period for the 22 matched subjects enrolled in the same program who didn't develop HCC.

"As we refine the process of detecting hypermethylated RASSF1A, we hope to have a functioning test for hepatocellular carcinoma," Chan said. "A significant number of people will develop this cancer and it is only through early screening and detection that we can hope to help them."

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org
In Atlanta (September 17-20):
404-221-6855

T vs. B: Re-engineered Human T Cells Effectively Target and Kill Cancerous B Cells

registration@aacr.org () — Tue, 18 Sep 2007 12:00:00 GMT

PHILADELPHIA - Human white blood cells, engineered to recognize other malignant immune cells, could provide a novel therapy for patients with highly lethal B cell cancers such as acute lymphoblastic leukemia (ALL), according to researchers at Memorial Sloan-Kettering Cancer Center (MSKCC). By administering repeated doses of T cells designed to express an artificial receptor which recognizes human B cells, the researchers were able to eradicate cancer in 44 percent of mice bearing human ALL tumors.

Their findings, published in the September 15 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, show that modified T cells - the white blood cells that actively fight infections - can be effective in fighting malignancies associated with B cells (immune cells that create antibodies) such as chronic lymphocytic leukaemia (CLL), ALL, non-Hodgkin's lymphoma (NHL). The researchers have an ongoing study using these T cells in CLL, and have recently begun the planning stages for a trial in patients with ALL.

"The immune system has evolved to police the body for infections and diseased cells, but it has a difficult time recognizing malignant cells since they largely appear normal to the immune system," said lead study author, Renier J. Brentjens, M.D., Ph.D., medical oncologist in the Leukemia Service at MSKCC. "The idea is that we can take a patient's own T cells, re-educate them by inserting a gene into them that will enable them to produce a receptor to recognize B cell cancers, and then return them to the patient where they should be able to attack and kill the tumor cells."

Because the technique uses a patient's own T cells, there is little risk of compatibility issues or rejection, as there might be with human stem cell transplant, Dr. Brentjens adds. Human stem cell transplant, following radiation or chemotherapy, is currently incorporated into the treatment of several B cell malignancies.

In order to get T cells to recognize B cells, Dr. Brentjens and his colleagues created a gene that encodes for a cell-surface protein - an artificial T cell receptor called a chimeric antigen receptor -- designed to specifically bind to CD19, a molecule found on the surface of B cells and B cell cancers. Antigen receptors are what allow T cells, in combination with other parts of the immune system, to recognize and attack infected or malignant cells. This chimeric gene, formed from active portions of several immune system-related genes, creates the chimeric antigen receptor protein called 19-28z, which does not require other co-stimulatory signals to fully activate T cells, according to Dr. Brentjens.

Dr. Brentjens and his colleagues used an engineered retrovirus to insert the chimeric antigen receptor gene into T cell DNA. Retroviruses insert DNA derived from their RNA into that of a host cell, which then uses viral vector-encoded genes to make specific proteins. In this case, the researchers infected healthy T cells with modified retroviruses containing the gene that codes for 19-28z. The T cell's internal protein-making facilities then produce the chimeric receptor as if it were one of its own natural antigen receptors.

In Clinical Cancer Research, the MSKCC researchers detail the creation of 19-28z, their "second generation" chimeric antigen receptor, and its effectiveness in stimulating human T cells both in culture and in an animal model of human cancer. They also compared T cells engineered with 19-28z to T cells engineered with a "first generation" chimeric antigen receptor, lacking the co-stimulatory signal found in 19-28z. Their results showed that the "second generation" 19-28z receptor was superior to the "first generation" receptor, and that this T cell therapy works best when administered to mice through multiple weekly injections.

"The repeated boosts of new T cells during therapy to improve T cell persistence enhances the efficacy of these T cells in eradicating cancerous B cells," said Dr. Brentjens. "This concept of T cell persistence being critical to treatment efficacy is one we are further investigating in current and upcoming clinical trials."

The results have given the researchers further evidence that the technique will work in humans. When transplanted back into a patient, these engineered T cells could then attack and kill tumor cells bearing the CD19 protein. "CD19 is not found on the surface of bone marrow stem cells, so these modified T cells are reasonably safe since they should not attack other blood forming cells in the bone marrow following treatment," Dr. Brentjens said.

Based on the results of their findings, the MSKCC researchers are currently conducting a clinical trial using this method in patients with chemotherapy-resistant CLL. CLL is currently considered an incurable cancer, Dr. Brentjens said, although the disease generally progresses slowly.

This research was funded by the Annual Terry Fox Run for Cancer Research, the Commonwealth Cancer Foundation for Research and the Experimental Therapeutics Center of MSKCC, the Alliance for Cancer Gene Therapy, an Amgen Career Development Award, The National Cancer Institute and the Bocina Cancer Research Fund.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

Scientists, Physicians Present Latest Findings in Translating Research Discoveries into “Personalized” Cancer Treatment and Prevention

registration@aacr.org () — Mon, 10 Sep 2007 12:00:00 GMT

AACR Convenes Second International Conference on Molecular Diagnostics in Cancer Therapeutic Development: Atlanta, Georgia, Sept. 17-20, 2007

PHILADELPHIA - Scientists and clinicians from around the world will gather in Atlanta, Georgia next week at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development. The conference is subtitled "Maximizing Opportunities for Personalized Treatment," which reflects the potential of molecular diagnostics to provide new strategies for tailoring therapies to fit the needs of each cancer patient's unique biology.

Sessions will include discussions on the use of biomarkers - blood-borne molecules that indicate the presence of cancer - in clinical practice and new drug development, advanced imaging technologies for diagnosis, and the application of proteomics in personalized medicine. Novel findings to be reported at the conference include:

Case studies that report how clinicians are already bridging the gap between basic cancer biology and personalized clinical care. Researchers present examples of how they fine-tuned the treatment of a number of different cancer types, including lung and ovarian, based on the genetic profile of the patient's tumors.
A new acoustic sensor device that could make it possible to screen for multiple cancer biomarkers during a routine doctor's visit.
A sensitive blood test for early-stage liver cancer that detects a gene altered by the molecular processes that lead to cancer.
A blood-borne protein, present in 99 percent of lung cancer patients tested, could provide a target for a simple blood test for the disease.

"As genetic, proteomic, imaging, and other new technologies become more sophisticated and our knowledge of tumor biology and signaling pathways advances, so too does our ability to molecularly characterize individual tumors and identify germline determinants of patient prognosis and response," said David Sidransky, M.D., meeting chairperson and professor of Otolaryngology - Head and Neck Surgery, Oncology, Pathology, Urology, and Cellular and Molecular Medicine at Johns Hopkins University School of Medicine and director, Head and Neck Cancer Research at The Johns Hopkins Hospital.

"This new era of personalized medicine has brought with it great opportunities to enhance cancer drug development and improve patient care," Dr. Sidransky said. "However, in order to harness this potential and maximize these opportunities, it is essential that there be an ongoing exchange of new ideas and information."

In addition to symposia and poster sessions, the conference will include a keynote lecture by Victor E. Velculescu, M.D., Ph.D., assistant professor in the Department of Oncology at Johns Hopkins University's Sidney Kimmel Comprehensive Cancer Center. Dr. Velculescu, a cancer genetics researcher, presents an address entitled "Blueprint of the Breast and Colorectal Cancer Genomes."

The AACR's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development will be held Sept. 17 - 20, 2007, at the Atlanta Hilton. For press registration and more information about the conference, please visit the press page.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Discovery Suggests Location of Genes for Breast Density, a Strong Risk Factor for Breast Cancer

registration@aacr.org () — Fri, 31 Aug 2007 12:00:00 GMT

PHILADELPHIA - Studying the DNA of 889 people, gene hunters at the Mayo Clinic and H. Lee Moffitt Cancer Centers have identified a region on chromosome 5p that is significantly associated with dense breast tissue, a known risk factor for breast cancer. The findings, published in the September 1 issue of Cancer Research, a publication of the American Association for Cancer Research, suggest that genes which influence breast density could serve as a predictive marker for disease and provide a biological target for agents that may reduce breast cancer risk by reducing breast density.

Women with dense breasts - meaning the breast has a smaller proportion of fat relative to stromal and epithelial tissues - are three to five times more likely to develop breast cancer than women with less dense breasts, according to the researchers. Scientists have estimated the total influence of genes on breast density to be about 60 percent.

The study, the first reported genetic linkage analysis for genes influencing breast density, "provides further evidence that this trait does appear to be genetically influenced," said the study's lead investigator, Celine Vachon, Ph.D., an epidemiologist at the Mayo Clinic in Rochester, Minnesota.

Although the investigators have strong evidence that a gene residing in this chromosomal region influences breast density, the exact gene that is responsible is not yet known. "One or more of the 45 candidate genes in this region could explain a large proportion of mammographic breast density, and potentially, breast cancer," she said.

Within the region on chromosome 5p, the gene which encodes the prolactin receptor in particular, stands out as a possible contributor to dense breasts. Prolactin is a hormone that helps enlarge mammary glands during pregnancy and, after childbirth, is involved in milk production. Previous research has found a correlation between mammographic density and prolactin levels in postmenopausal women, the researchers note.

Vachon's team took what they term an "agnostic" approach to uncovering genes, or gene regulators like microRNA, that are involved in the development of dense breasts. "We assume we don't know anything about the biology of the trait and we let the genomes of our participants and their breast densities guide us," Vachon said.
Their method contrasts the traditional "candidate gene" approach, where scientists look at variations in specific genes thought to be involved with the disease or trait of interest. Such linkage studies have been used to uncover many high-impact risk genes, such as the breast cancer susceptibility genes BRCA1 and BRCA2.

The Mayo researchers performed a genome-wide linkage scan to identify possible chromosome regions in 89 families, part of a multi-generational Minnesota family study that began in 1944 at the University of Minnesota. Blood samples and mammograms were collected and analyzed for 756 female participants; 133 men were also included to help clarify genetic information in their offspring, mothers and sisters. "We used the relationship between family members and breast density to inform where a gene might be," Vachon says.

Researchers first studied 403 DNA markers spaced across the genome to determine the amount of genetic information shared at and between each of these genomic signposts and its correlation to breast density as measured on mammography. They found three regions of interest, and narrowed the most promising region further by studying 21 additional, more densely spaced DNA markers. This secondary analysis highlighted one region consisting of approximately 45 known genes on chromosome 5p that was significantly associated with increased breast density.

The researchers then adjusted their analysis to eliminate the contribution of body mass index (BMI), which is a known breast cancer risk factor and also inversely associated with breast density, and found the "signal" was just as strong. "That means the location that we have identified on chromosome 5p does not appear to affect breast density through its influence on BMI," she said.

Only age, diagnosis of abnormal cells on a breast biopsy and inheritance of rare breast susceptibility genes, such as BRCA1 and BRCA2, are stronger risk predictors of breast cancer than is breast density, Vachon said.

"At this point, we have not identified a gene or genes for breast density but a promising location to investigate further," Vachon said. "Identification of genes for breast density will improve our understanding of how breast density influences breast cancer development in women."

"In this study we focused on the genetics of a risk factor for cancer. This approach has not been tried before," said Thomas Sellers, Ph.D., a coauthor on this study and currently director of the Moffitt Research Institute in Tampa, Florida.

The study was funded by a grant from the National Cancer Institute.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; healthcare professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Nominations Open for AACR’s Scientific Awards, Lectureships

registration@aacr.org () — Thu, 23 Aug 2007 12:00:00 GMT

Nomination deadline: Monday, October 1, 2007

PHILADELPHIA - Continuing a nearly 50-year-old tradition of honoring outstanding achievement in cancer research, the American Association for Cancer Research (AACR) currently is accepting nominations for its series of annual awards and lectureships. Scientists advancing the understanding and eradication of cancer through basic research, clinical care, therapeutics and prevention are eligible. Winners will help the AACR fulfill its mission to promote professional education and communication by delivering a lecture during the AACR Annual Meeting, April 12-16, 2008, in San Diego, Calif.

The fields and corresponding awards are:

Innovative cancer research and collaborations:
AACR Princess Takamatsu Memorial Lectureship, to recognize an individual scientist whose novel and significant work has had or may have a far-reaching impact on the detection, diagnosis, treatment or prevention of cancer, and who embodies the dedication of Her Imperial Highness Princess Kikuko Takamatsu of Japan to multinational collaborations.

Basic cancer research:
AACR-G.H.A. Clowes Memorial Award, in honor of a founding member of the AACR, the award recognizes an individual with outstanding recent accomplishments in basic cancer research.

Translational cancer research:
AACR-Richard and Hinda Rosenthal Foundation Award, recognizes notable contributions on the part of medical practitioners aged 50 or younger who reside in the Americas. The award provides incentives to young investigators relatively early in their careers.

Clinical cancer research:
AACR-Joseph H. Burchenal Clinical Research Award, recognizes outstanding achievements in clinical cancer research. It is named for Dr. Joseph H. Burchenal, Past President of the AACR, and a major figure in clinical cancer research and chemotherapy.

Chemistry:
AACR-CICR Award for Outstanding Achievement in Chemistry in Cancer Research, for outstanding, novel, and significant achievements in chemistry which have led to important contributions to the fields of basic cancer research; translational cancer research; cancer diagnosis; the prevention of cancer; or the treatment of patients with cancer.

Young investigators:
AACR Award for Outstanding Achievement in Cancer Research, recognizes a young investigator, 40 years of age or younger, on the basis of meritorious achievement in cancer research.

Epidemiology, biomarkers and prevention:
AACR-American Cancer Society Award for Research Excellence in Cancer Epidemiology and Prevention, established in 1992 to honor outstanding research accomplishments in the fields of cancer epidemiology, biomarkers, and prevention.

Advancement of women in science:
AACR-Women in Cancer Research-Charlotte Friend Memorial Lectureship, named for the renowned virologist and discoverer of the Friend virus, this lecture provides recognition for an outstanding scientist who has made meritorious contributions to the field of cancer research and who has, through leadership or by example, furthered the advancement of women in science.

Advancement of minority investigators in cancer research:
AACR-Minorities in Cancer Research-Jane Cooke Wright Lectureship, first presented in 2006, the lectureship is intended to recognize an outstanding scientist who has made meritorious contributions to the field of cancer research and who has, through leadership or by example, furthered the advancement of minority investigators in cancer research.

Since 1961, when the first scientific award was presented, the AACR has honored hundreds of scientists and physicians, who collectively have made significant contributions to the understanding, diagnosis, prevention and treatment of cancer.

For more information on the nomination process and other details about the awards and lectureships, please visit the Scientific Achievement Awards page. Inquiries regarding these awards should be directed to eversley@aacr.org.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Media Contact:
Yarissa Ortiz
215-440-9300, Ext. 101
ortiz@aacr.org

Award Information:
Monique Eversley
215-440-9300, Ext. 274
eversley@aacr.org

The Association of Obesity and Lack of Exercise with the Risk of Pancreatic Cancer May be Mediated by a Protein in the Blood

registration@aacr.org () — Wed, 15 Aug 2007 12:00:00 GMT

PHILADELPHIA - Obesity and aversion to exercise have become hallmarks of modern society - and a new study suggests that a blood protein linked to these lifestyle factors may be an indicator for an increased risk of developing pancreatic cancer. Researchers from the Dana Farber Cancer Institute report their findings in the August 15 issue of Cancer Research, a journal of the American Association for Cancer Research.

In a study of 144 patients with pancreatic cancer and 429 people without the disease, a subset of patients with low blood levels of a protein called IGFBP-1 were at approximately twice the risk of developing pancreatic cancer. Low blood levels of this protein have previously been linked to excess weight and lack of physical activity. Their data originated from tens of thousands of men and women enrolled in four large-scale cohort studies - the Health Professionals Follow-Up Study, the Nurses' Health Study, the Physicians' Health Study and the Women's Health Initiative Observational Study - all of which followed the health of participants over numerous years.

"The prognosis for many patients with pancreatic cancer remains poor, so it is vitally important that we indentify and better understand risk factors for the disease, particularly risk factors that are modifiable" said lead study author, Brian M. Wolpin, M.D., attending physician at Dana Farber Cancer Institute. "In addition to cigarette smoking, exercise and weight control appear to be important modifiable risk factors for this difficult disease."

Pancreatic cancer is one of the leading causes of cancer death in America - over 33,000 Americans will likely die from the disease in 2007, according to projections from the American Cancer Society. Studies indicate that smoking is responsible for about 25 percent of pancreatic cancer cases, and obesity and lack of exercise may account for a similar amount, Dr. Wolpin said.

According to Dr. Wolpin, previous research has linked IGFBP-1 (insulin-like growth factor binding protein one) with increased risk of colorectal and endometrial cancer. Like its name suggests, IGFBP-1 is a molecule that binds with insulin-like growth factor (IGF), a hormone normally associated with growth and development. In the laboratory, IGF has been noted to increase the growth of pancreatic cancer cells. Since one role of IGFBP-1 is to sequester IGF, Dr. Wolpin and his colleagues were interested as to whether people who developed pancreatic cancer had lower blood levels of the IGFBP-1 protein.

To study the relationship between IGFBP-1 and pancreatic cancer, Dr. Wolpin and his colleagues chose pancreatic cancer patients enrolled in one of the four cohort studies and with blood drawn four or more years before developing cancer. The blood levels of IGFBP-1 from these patients were compared to those taken from 429 cancer-free people also enrolled in one of the cohort studies. According to their findings, patients with low blood levels of IGFBP-1 were nearly twice as likely to develop pancreatic cancer.

"We still have much to learn about the mechanisms by which obesity and sedentary lifestyle may contribute to the risk of pancreatic cancer," Dr. Wolpin said. "While it is too early to discuss IGFBP-1 as a suitable blood marker for pancreatic cancer, it is never too early to address the lifestyle issues that may contribute to low levels of IGFBP-1 and to an elevated risk of this difficult disease."

The study was supported by The Lustgarten Foundation for Pancreatic Cancer Research and the National Cancer Institute.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Green Tea Boosts Production of Detox Enzymes, Rendering Cancerous Chemicals Harmless

registration@aacr.org () — Fri, 10 Aug 2007 12:00:00 GMT

PHILADELPHIA - Concentrated chemicals derived from green tea dramatically boosted production of a group of key detoxification enzymes in people with low levels of these beneficial proteins, according to researchers at Arizona Cancer Center.

These findings, published in the August issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, suggest that a green tea concentrate might help some people strengthen their metabolic defense against toxins capable of causing cancer.

In a study of 42 people, the concentrate - composed of chemicals known as green tea catechins in amounts equal to that found in 8-16 cups of green tea - boosted production of the enzymes, which belong to the glutathione S-transferase (GST) family, by as much as 80 percent in some participants.

GST enzymes are believed to be crucial to the body's defense against cancer-causing chemicals and other toxins, according to the study's lead investigator, H.-H. Sherry Chow, Ph.D., a research associate professor at the University of Arizona. They modify the cancer-causing molecules that would otherwise damage cellular DNA, thus rendering them inert.

"They actually convert known carcinogens to non-toxic chemicals, and studies have shown a correlation between deficient expression of these enzymes and increased risk of developing some cancers," Chow said.

"Expression of this enzyme varies dramatically in people due to genetic variation and environmental factors," Chow added. "Green tea catechins somehow increase gene expression of these enzymes, which can be an advantage to people with low levels to start with."

Green tea has long been of interest to researchers given studies that have shown populations in which it is often consumed, such as the Chinese and Japanese, generally have lower rates of cancer. To find out if green tea can protect against cancer, the NCI has sponsored a number of rigorous scientific studies testing capsules of the extract, Polyphenon E, that have been prepared in Japan to meet exact specifications. These pills contain epigallocatechin gallate (EGCG), a catechin known for its potent antioxidant activity, and are currently being tested against a variety of cancers in clinical trials.

This study was designed to see if green tea catechin concentrate had any effect on the levels of GST enzymes in healthy individuals - research that could explain the tea's anti-cancer properties. Healthy volunteers were asked to abstain from consuming any tea or tea-related products for four weeks. At the end of this "washout period," blood was drawn and baseline GST enzyme levels were determined for each participant. Then, the volunteers were asked to take four Polyphenon E capsules, for a total of 800 milligrams of EGCG, each morning on an empty stomach for four weeks and to abstain from drinking tea or eating many cruciferous vegetables, which contain other beneficial chemicals. Another blood sample was taken after four weeks, and GST activity was determined.

Researchers found that use of Polyphenon E enhanced GST activity when data from all participants were included for analysis. But it had its most significant effect in volunteers whose baseline blood measurements showed low GST activity - an 80 percent increase compared to baseline GST activity. Activity did not change in volunteers with medium GST expression, or in those with the highest levels, GST seemed to decrease slightly although researchers believe that decline was due to random variation.

"This is the first clinical study to show proof that chemicals in green tea can increase detoxification enzymes in humans," Chow said. "There may be other mechanism in play by which green tea may protect against cancer development, but this is a good place to start."

The NCI supported the study and researchers from NCI also participated in conducting the study.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Smokeless Tobacco More Effective than Cigarettes for Delivering Dangerous Carcinogens into the Body, Researchers Say

registration@aacr.org () — Thu, 09 Aug 2007 12:00:00 GMT

PHILADELPHIA - It may not be inhaled into the lungs, but smokeless tobacco exposes users to some of the same potent carcinogens as cigarettes. In the August issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, researchers at the University of Minnesota Cancer Center report that users of smokeless tobacco are exposed to higher amounts of tobacco-specific nitrosamines -- molecules that are known to be carcinogenic -- than smokers.

Smokeless tobacco, also known as oral snuff, is a variant on chewing tobacco that users suck on by slipping it between their cheeks and gums. In a study comparing 182 oral snuff users with 420 cigarette smokers, the Minnesota researchers found that snuff users were exposed to higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) than smokers. NNK is a human carcinogen known to produce lung cancer as well as cancers of the pancreas, nasal mucosa and liver in laboratory animals.

"Smokeless tobacco products have been proposed by some as safer alternatives to cigarettes, but they are not safe," said author Stephen S. Hecht, Ph.D., professor of cancer prevention at the University of Minnesota Cancer Center. "The only likely safe alternative to smoking is the long term use of nicotine replacement therapy as a means to reduce dependence."

"In fact, this study lends evidence to support the notion that the oral use of tobacco actually provides a more efficient means for delivering certain carcinogens into the body through the bloodstream, although cigarette smoke includes a host of carcinogenic products that aren't a major factor in smokeless tobacco," Hecht said.

The study participants included men and women aged 17 to 80 who had sought - but had yet to begin - treatment for tobacco addiction, and who used conventional, popular U.S. brands of smokeless tobacco. The researchers studied nitrosamine exposure by analyzing the urine of participants for NNAL, a biomarker for NNK exposure, as well as cotinine, a biomarker for nicotine. Hecht and his colleagues found that both cotinine and NNAL levels were higher in the urine of snuff users than smokers, when adjusted for age and gender.

According to Hecht, the nitrosamines found in tobacco, including NNK, are byproducts of the curing process involved in turning tobacco leaves into products like cigarettes, chew and snuff. While "low nitrosamine" smokeless tobacco products are available, including a Swedish-style product known as "snus," these still contain NNK and other nitrosamines.

"American smokeless tobacco manufacturers are forbidden by federal law from claiming that smokeless tobacco is a safer alternative to smoking," Hecht said. "That does not prevent them from advancing the general concept that snuff can be used as a substitute for cigarettes, especially in places, like an office setting, where snuff may be acceptable while smoking is not."

This study was funded by the National Institutes on Drug Abuse, the National Cancer Institute, and the American Cancer Society.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

No Evidence That Widely Prescribed Statins Protect Against Prostate Cancer

registration@aacr.org () — Thu, 09 Aug 2007 12:00:00 GMT

PHILADELPHIA - A large community-based study refutes previous findings that statins - a top-selling drug class, worldwide -- might cut one's risk of developing prostate cancer by reducing production of the male hormones that fuel cancer growth.

Researchers from the New England Research Institutes found that while men using statins did indeed have lower blood levels of androgens such as testosterone, it was more likely attributable to poor health rather than the use of statins. Their findings are published in the August issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

"The public health significance is that our study provides evidence that statins may not have a clinically meaningful impact on testosterone in the blood, although further studies should be done," said study author, Susan A. Hall, Ph.D., a research scientist at the New England Research Institutes. "That doesn't mean that statins may be lowering prostate cancer risk through one or more alternative pathways, but it doesn't appear to be working through reduction of male hormones.

Statins lower cholesterol and are commonly prescribed to treat and prevent heart disease. Since cholesterol is required for the production of male hormones researchers have theorized that statins may reduce production of these hormones. A large, recent study found that men using statin drugs were at lowered risk of developing metastatic or fatal prostate cancer, especially if the drugs were used over a long period of time. But other studies on statin use and prostate cancer risk have had mixed results, according to Hall.

To study a narrow question - whether statin use reduces androgen concentrations in the blood - the researchers examined data from the Boston Area Community Health (BACH) survey, a population-based, NIH-sponsored, epidemiologic study. Data were collected between 2002 and 2005 on thousands of men and women with equal representation of African American, Caucasian and Hispanic populations.

The value of the BACH study, according to Hall, is that "we capture real world use of medications in the community, which might be a more realistic representation of their impact on the body, compared to outcomes seen in a clinical trial."

Hall's team studied the medical histories of 1,812 men, including 237 statin users, and analyzed their blood for "free" or unbound testosterone, for total testosterone, and for other associated compounds.

The researchers found no relationship between statin use and free testosterone and most of the other associated compounds. There was a significant association between statin use and level of total testosterone in the blood, but that association vanished when researchers considered the patients' age, body weight, and history of cardiovascular disease and diabetes. "We know that men with higher body mass index, diabetes and cardiovascular disease tend to have lower testosterone levels, and this largely accounted for the drop in testosterone in statin users," Hall said.

"In this study, statin use was just a marker for presence of other illnesses," she said. "This study may inform that debate, however, by suggesting that any protective pathway offered by statins, if it exists, is not through androgen suppression."

The BACH Survey was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Phase II Study of Therapeutic Vaccine Shows Efficacy in Patients with Metastatic Colorectal Cancer

registration@aacr.org () — Wed, 01 Aug 2007 12:00:00 GMT

PHILADELPHIA - A therapeutic cancer vaccine has shown effectiveness when given alongside chemotherapy to patients with metastatic colorectal cancer in a phase II trial, according to researchers at Oxford BioMedica (UK) Ltd. The study found that six of the 17 metastatic colorectal cancer patients in the study showed tumor shrinkage, classified as complete or partial responses following independent expert review.

The study, reported in the August 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, was designed to demonstrate the safety and immunogenicity of the vaccine, called modified vaccinia Ankara-encoding 5T4 (TroVax®), when used alongside standard chemotherapy. The research was funded by Oxford BioMedica which is developing the vaccine in partnership with Sanofi-Aventis.

Unlike preventative vaccines, such as the human papillomavirus vaccine to prevent cervical cancer, TroVax is a therapeutic vaccine, designed to stimulate the immune systems of patients who already have cancer. The vaccine consists of an attenuated (non-disease causing) version of the vaccinia virus modified to deliver the gene for 5T4, a protein found in many tumors.

"The idea is that the modified virus enters cells, produces the tumor protein and stimulates the immune system," said lead study author Richard Harrop, Ph.D., vice president of clinical immunology at Oxford BioMedica. "To give a vaccine alongside chemotherapy might seem counterintuitive, since chemotherapy can weaken the immune system, but our study shows that TroVax could be complementary to standard chemotherapy, enhancing the immune response to tumors."

The target of this immuno-therapy approach is a tumor antigen called 5T4, a protein embedded within the membrane of cancer cells. The protein is rarely found in normal tissues, but is produced at high levels by a wide range of human cancers, including colorectal, renal, gastric and ovarian. The production of 5T4 has been associated with cancer metastasis and poor prognosis for patients.

"Typically, the immune system doesn't pay attention to this molecule, so by producing 5T4 artificially in combination with the ‘danger signals' associated with a viral infection, we are demanding that the immune system take notice," Harrop said. "TroVax causes cells at the injection site to produce 5T4 in a way which agitates the immune system into producing antibodies and killer T cells. It is hoped that these two components of the immune system then migrate to tumors and kill them without harming any normal tissues."

"In essence, it's like turning up your stereo in the hopes that it will attract the police to your neighbor's rowdy party," Harrop said.

Harrop and his colleagues administered the vaccine to 17 patients with metastatic colorectal cancer just before, during and after the patients were treated with the standard chemotherapy regimen FOLFOX which consists of the agents: 5-fluorouracil, folinic acid and oxaliplatin.

Through the course of the study, the researchers monitored the patients for an immune response to 5T4. Eleven of the 17 patients who received the complete course of vaccinations (six injections) mounted strong immune responses to the 5T4 tumor protein. Of these 11 patients, six exhibited significant shrinkage of their tumors and one patient no longer had any detectable tumors. Researchers noted no complications stemming from TroVax vaccination or any other evidence that would call into question the safety of the vaccine.

While the study was not designed to prove that patients survived longer than would normally be expected, the researchers noted that, on average, the overall median survival was 68 weeks in all 17 vaccinated patients and 118 weeks in the 11 patients who received all six vaccinations.

According to Harrop, the researchers are currently testing the vaccine in a phase III trial in renal cancer patients in the U.S. and Europe and Sanofi-Aventis is planning a phase III study in colorectal cancer.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-656-0554
lester@aac.org

COX-2 Inhibitors Delay Pancreatic Cancer Precursors in Mice

registration@aacr.org () — Wed, 01 Aug 2007 12:00:00 GMT

PHILADELPHIA-- Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor, delays the progression of precancerous pancreatic lesions in mice, according to researchers at David Geffen School of Medicine at UCLA. While inflammation has been shown to be a factor in many forms of cancer, the researchers say this is the first study to demonstrate the effect of an anti-inflammatory COX-2 inhibitor on the development of pancreatic cancer.

The study, published in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, suggests a potential role for COX-2 inhibitors in pancreatic cancer prevention among high-risk patients. Pancreatic cancer is one of the leading causes of cancer death in America - over 33,000 Americans will likely die from the disease in 2007, according to projections from the American Cancer Society.

"By inhibiting COX-2 in human patients, we may have an option to delay the progression of lesions," said lead author Guido Eibl, M.D., scientific director of the Hirshberg Laboratory of Pancreatic Cancer Research and adjunct assistant professor at UCLA.

Researchers believe pancreatic cancer arises from abnormal tissues, or lesions in the pancreas, known as pancreatic intraepithelial neoplasias (PanINs). By stalling the growth of PanINs, researchers hope to slow the development of or prevent pancreatic cancer.

COX-2, an enzyme which causes inflammation, is no stranger to cancer researchers. Studies of breast, colon, and pancreatic cancers have led researchers to believe COX-2 plays a key role in the development and growth of tumors.

To study the effects of COX-2 on PanIN progression, Dr. Eibl and colleagues focused on the KrasG12D mouse, an animal model that mimics the early stages of pancreatic cancer. In the KrasG12D mouse, low-grade PanINs (stage I or II) begin to appear in the pancreas of mice at one month. Starting at six months, high-grade PanINs (stage III) can be found in the mouse pancreas. According to Dr. Eibl, most researchers agree that stage III PanINs are a direct precursor to pancreatic cancer in humans as well as mice. Between 12 and 15 months, Dr. Eibl says the majority of KrasG12D mice will develop pancreatic tumors.

The UCLA researchers divided the mice into two groups - one set received a nimesulide-enriched diet for 10 months; the other was offered only regular mouse chow. Their analyses revealed that the nimesulide diet greatly reduced the number of late-stage PanINs in KrasG12D (10 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on nimesulide diet versus 40 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on normal diet).

Because the pancreases of mice were analyzed at 10 months, before the typical appearance of pancreatic tumors, additional studies will be needed for researchers to conclude whether or not nimesulide can delay the onset of or prevent pancreatic cancer.

"With these results, I certainly wouldn't say everyone should be taking COX-2 inhibitors to protect against cancer," said Eibl. "However, with additional studies, we may find COX-2 inhibitors could help prevent pancreatic cancer in high risk populations."

"Pancreatic cancer is so deadly because it often goes undetected until it's too late," said Dr. Eibl. "If a patient is at a high-risk for developing pancreatic cancer, a COX-2 inhibitor may offer some protection."

In the future, Dr. Eibl and others plan to study the long-term effects of nimesulide and additional COX-2 inhibitors on the onset and progression of pancreatic cancer.

This study was funded by the National Institutes of Health, the Jonsson Cancer Center Foundation at UCLA, and the Hirshberg Foundation for Pancreatic Cancer Research.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

New Minimally Invasive Sampling Technique Allows for Earlier Diagnosis of Pancreatic Cancer

registration@aacr.org () — Wed, 01 Aug 2007 12:00:00 GMT

PHILADELPHIA - A new optical technology, coupled with routine endoscopy, may enable doctors to detect the subtle tell-tale traces of early pancreatic cancer, according to researchers at Northwestern University in Illinois. The optical technology, developed by biomedical engineers at Northwestern exposes cellular changes indicative of cancer in tissue near the pancreas that had previously been detectable only through intensive radiologic scanning or invasive surgery, two techniques that can put pancreatic cancer patients at risk.

The results of the pilot study, presented in the August 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, could represent a new approach to detecting pancreatic cancer at a very early stage, when treatment is most likely to succeed.

"Pancreatic cancer is not often detected early because it is a rather inaccessible organ, so this technique holds the potential to be the first reliable, routine screening tool for pancreatic cancer," said co-author Randall Brand, M.D., an associate professor of medicine at Northwestern University and clinician at Evanston Northwestern Healthcare. "If we could apply this to those at high risk - such as people with chronic pancreatitis or who have a family history of pancreatic cancer- we might see a drastic improvement in pancreatic cancer survival."

Pancreatic cancer is one of the leading causes of cancer death in America - over 33,000 Americans will likely die from pancreatic cancer in 2007, according to projections from the American Cancer Society. The five-year survival rate for pancreatic cancer is less than five percent of all cases. However, if caught at an early stage, available treatments cause the five-year survival rate to jump 10-fold to 50 percent, Dr. Brand said.

Although the pancreas is a difficult organ to study, the researchers took advantage of the so-called "field effect" of pancreatic cancer, where cancerous tissue exerts subtle physical changes in surrounding tissue. In an examination of 51 patients using tissue sampled through upper endoscopy (a minimally invasive procedure that entails the placement of an endoscope down the throat and through the stomach to the duodenum), the researchers were able to identify those patients with pancreatic cancer from the control group with a 95 percent accuracy. Importantly, the researchers could identify all 10 patients with early stage tumors that could be removed surgically.

"If we could reliably detect the presence of cancer prior to our ability to visualize it with our current imaging studies such as a CT scan or MRI, we would then have the justification to pursue aggressive surgical options," Dr. Brand said.

The optical technology used to detect the field effect of pancreatic cancer was developed by the senior author of the study Vadim Backman, Ph.D., a professor of biomedical engineering at Northwestern along with his graduate student, Yang Liu, Ph.D, the first author on the report. With a single instrument, Backman can use two different means of detecting the optical properties of a tissue sample, both of which were developed in his laboratory: four-dimensional elastic light scattering fingerprinting (4D-ELF) and low-coherence enhanced backscattering spectroscopy (LEBS).

In essence, the 4D-ELF/LEBS instrument shines an intense white light onto a tissue sample and then measures how cellular structures on the micro- or nanoscale (on the order of a billionth of a meter) refract the light, causing it to scatter in different directions. Computer analysis of the scatter patterns can then determine if these cellular structures are different than those seen in structures within "normal" tissue. The researchers looked for the same optical changes that had been identified in a colorectal cancer study by Backman and Hemant Roy, M.D., an associate professor at Northwestern University and clinician at Evanston Northwestern Healthcare.

"We are able to use the optical properties of a cell's structure to serve as a marker for disease," said Backman. "These are changes within the tissue that cannot be detected through any other means. Neither antibodies nor diagnostic assays can detect them."

According to Backman, optical markers are independent of other factors within the tissue microenvironment. "The markers do not change if the patient is a smoker. And the markers do not change with the location, stage or size of the tumor in the pancreas," Backman said.

With the success of the pilot study, the researchers are currently involved in a larger study of the technique and its refinement. They estimate that the technology may be put into practice within three years.

Additional co-authors include Vladimir Turzhitsky and Young Kim of Northwestern University and Hemant Roy, Nahla Hasabou, Charles Sturgis, Dhiren Shah and Curtis Hall of Evanston-Northwestern Healthcare.

The study was supported by funding from the National Science Foundation and the National Institutes of Health.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Marijuana Component Opens the Door for Virus That Causes Kaposi’s Sarcoma

registration@aacr.org () — Wed, 01 Aug 2007 12:00:00 GMT

PHILADELPHIA - The major active component of marijuana could enhance the ability of the virus that causes Kaposi's sarcoma to infect cells and multiply, according to a team of researchers at Harvard Medical School. According to the researchers, low doses of Δ-9 tetrahydrocannabinol (THC), equivalent to that in the bloodstream of an average marijuana smoker, could be enough to facilitate infection of skin cells and could even coax these cells into malignancy.

While most people are not at risk from Kaposi's sarcoma herpes virus (KSHV), researchers say those with lowered immune systems, such as AIDS patients or transplant recipients, are more susceptible to developing the sarcoma as a result of infection. Their findings, reported in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, offer cautionary evidence that those with weakened immune systems should speak with their doctors before using marijuana medicinally or recreationally.

"These findings raise some serious questions about using marijuana, in any form, if you have a weakened immune system," said lead study author Jerome E. Groopman, M.D., professor of medicine at Harvard Medical School. "While THC is best known as the main psychotropic part of marijuana, an analog of THC is the active ingredient of marinol, a drug frequently given to AIDS patients, among others, for increasing appetite and limiting chemotherapy-induced nausea and vomiting."

While previous studies indicated that marijuana smoking was associated with Kaposi's sarcoma, this is the first to demonstrate that THC itself can assist the virus in entering endothelial cells, which comprise skin and related tissue.

According to Dr. Groopman, the study illustrates the complicated role marijuana and other cannabinoids play in human health. Numerous types of cells display cannabinoid receptors on their outer surfaces, which act as switches that control cellular processes. Dr. Groopman's laboratory had previously demonstrated that THC could have a protective effect against a certain form of invasive, drug-resistant lung cancer.

To study the combined effect of THC and KSHV, the researchers examined a culture of human skin cells, which are susceptible to infection and could provide a model of Kaposi's sarcoma. These culture cells display many copies of two prominent cannabinoid receptors. Dr. Groopman and his colleagues found that by bonding to these receptors, low doses of THC activate two proteins responsible for maintaining a cell's internal framework, or cytoskeleton. By altering the cytoskeleton, THC effectively opens the door for KSHV, allowing the virus to more easily enter and infect the cell. "We can take away that effect by using antagonists that block the two cannabinoid receptors, which adds evidence that THC is the culprit," Dr. Groopman said.

Once a cell is infected, the presence of THC may also promote the cellular events that turn it cancerous, the researchers say. They found that THC also promotes the production of a viral receptor similar to one that attracts a cell-signaling protein called interleukin-8. Previous studies have noted that this receptor could trigger the cell to reproduce, causing Kaposi's sarcoma-like lesions in mice. Indeed, the researchers saw that THC induced the infected cells to reproduce and form colonies in culture.

"Here we see both infection and malignancy going on in the presence of THC, offering some serious concerns about the safety of THC among those at risk," Dr. Groopman said. "Of course, we still do not know the exact molecular events that are occurring here, but these results are just the first part of our ongoing research."

The study was funded by the National Institutes of Health.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Nominations Open for 2008 Pezcoller Foundation-American Association for Cancer Research International Award for Cancer Research

registration@aacr.org () — Tue, 31 Jul 2007 12:00:00 GMT

Nomination Deadline: Friday, September 14, 2007

PHILADELPHIA - Scientists involved in cancer research, cancer medicine, or cancer-related biomedical science can nominate a colleague or professional associate for the 10th Pezcoller Foundation-AACR International Award for Cancer Research. The award was established in 1997 to annually recognize a scientist:

Who has made a major scientific discovery in basic cancer research or who has made significant contributions to translational cancer research;
Who continues to be active in cancer research and has a record of recent, noteworthy publications; and
Whose ongoing work holds promise for continued substantive contributions to progress in the field of cancer.

While intended to honor an individual, more than one scientist may be co-nominated and selected to share the award if their investigations are closely related in subject matter.

The Award consists of €75,000 and a commemorative plaque. The winner will give an award lecture during the 2008 AACR Annual Meeting, April 12-16 in San Diego, Calif., and will officially receive the award at a May 2008 ceremony in Trento, Italy, where the Pezcoller Foundation is located.

For more information on the nomination process and other details about the award please click here. Inquiries regarding this award should be directed to eversley@aacr.org.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Media Contact:
Yarissa Ortiz
215-440-9300, Ext. 101
ortiz@aacr.org

Award Information:
Monique Eversley
215-440-9300, Ext. 274
eversley@aacr.org

Adult Survivors of Childhood Leukemia Exercise Less, Worsening Already High Risk for Obesity and Illness

registration@aacr.org () — Mon, 23 Jul 2007 12:00:00 GMT

PHILADELPHIA -- Overcoming pediatric cancer may only mark the beginning of a young survivor's lifelong battle to stay healthy. While survivors of childhood acute lymphoblastic leukemia (ALL) face an increased risk of developing serious health complications as a result of their cancer treatment, for a variety of reasons many avoid simple exercise and healthy lifestyle changes that could reverse the damage, according to a team of researchers based at Memorial Sloan-Kettering Cancer Center.

Adult survivors of childhood ALL are less physically active than the general U.S. population, the team reports in the July issue of Cancer Epidemiology, Biomarkers, & Prevention, a journal of the American Association for Cancer Research. Furthermore, adult survivors of ALL who received cranial radiotherapy (CRT), or "whole brain radiation," as children reported the lowest activity among all adults, suggesting that the type of therapy administered to a child may impair his or her physical activity in the future.

To protect adult childhood cancer survivors from a future of disease, researchers say patients should work with health care providers to develop plans for healthier and more active lifestyles.

"Research shows that physical activity can undo risk caused by treatment," said senior author Kevin C. Oeffinger, M.D., from Memorial Sloan-Kettering Cancer Center, New York, N.Y. "Small, incremental steps can make a big difference in improving health outcomes."

Dr. Oeffinger and his colleagues compared the physical activity levels of over 2,600 adult survivors of ALL, ages 18 to 44, as reported by patients in the Childhood Cancer Survivor Study (CCSS) in 2003, to physical activity of age-matched adults in the general U.S. population, as reported in the 2003 Behavioral Risk Factor Surveillance System (BRFSS) survey. The CCSS is a multi-institution study sponsored by the National Cancer Institutes, and the BRFSS is a state-based survey conducted by the Centers for Disease Control (CDC). In both surveys, study participants were asked to report the number of times they had participated in physical activity or exercise during the prior month.

The study found that adult ALL survivors were less likely to meet the CDC physical activity guidelines (52.8 percent vs. 48.2 percent) and more likely to report no moderate or vigorous physical activity during the month preceding the survey (23 percent vs. 20.3 percent), with the highest levels of physical inactivity in ALL survivors who had received CRT treatment. Women who were treated with a moderate dose of CRT were twice as likely to be physically inactive as women in the general population.

"It's important to remember that these patients are not couch potatoes or lazy," said Dr. Oeffinger. "Our findings suggest that CRT has fundamentally altered something in the central nervous system that's leading to a decrease in levels of physical activity."

Because exercise reduces the risk of developing cardiovascular diseases, the CDC advises Americans to engage in a minimum of 30 minutes of moderate physical activities such as brisk walking, gardening, or vacuuming five days per week, or vigorous physical activities such as running, aerobics, or heavy yard work three days per week. While more than half of the U.S. population fails to meet CDC recommendations, low physical activity among adult survivors of ALL may further increase this group's already high risk for obesity, cardiovascular disease and mortality, researchers said.

Though the addition of CRT to ALL therapy over 40 years ago led to a marked increase in survival rates, research has since linked CRT to reduced cognitive function, hormonal imbalance and obesity. In some patients, CRT may cause loss of postural and motor control, balance, and/or muscle weakness, which may lead to decreased physical activity.

Because of the risks associated with CRT and the availability of improved chemotherapy drugs to treat ALL, CRT is now only used to treat children with particularly aggressive forms of ALL. According to Dr. Oeffinger, approximately 10 to 15 percent of ALL patients today are treated with CRT.

Although childhood cancer patients are less likely to receive CRT than they were 20 years ago, Dr. Oeffinger says modern chemotherapy for ALL may also lead to decreased levels of physical activity, and needs further study. To reduce the long-term negative effects of chemotherapy on childhood cancer survivors, researchers hope to teach children and their families healthy lifestyle habits early, so they can carry them into adulthood.

"The storyline is that physical inactivity and obesity outcomes are based upon type of therapy administered to patient," said Dr. Oeffinger. "Importantly, there are things we can do to intervene and to help childhood cancer survivors to regain active lifestyles that will protect the patient in the long run."

This research was funded by the Department of Health and Human Services, the Children's Cancer Research Fund, the American Lebanese Syrian Associated Charities, and the University of Rochester School of Medicine.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Obesity Found to be a Risk Factor for Multiple Myeloma

registration@aacr.org () — Thu, 19 Jul 2007 12:00:00 GMT

PHILADELPHIA - An obese person is more likely than a lean person to develop multiple myeloma, according to researchers from Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health. Their findings indicate that Body Mass Index (BMI) - a statistical measure that scales weight to height - provides an indicator for one's risk of developing multiple myeloma, a cancer of the blood cells that produce antibodies. Multiple myeloma currently affects more than 50,000 people in the U.S., and the five-year survival rates of the cancer are below 40 percent.

The study, published in the July issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, takes its data from over 100,000 participants in the on-going Nurses' Health Study and Health Professionals Follow-up Study, two similar large-scale studies. The study findings were similar to those from previously published studies that included smaller numbers of multiple myeloma patients, and/or were based on a one-time recording of height and weight.

"I find the results of these studies encouraging, since they show consistent results about the first risk factor for multiple myeloma that people can actually modify," said the study's lead author Brenda M. Birmann, Sc.D., a researcher in the Department of Medicine at Brigham and Women's Hospital and Harvard Medical School. "Treatment options for this disease are improving, but it is also important to identify risk factors that could be modified. We would like to learn how to prevent its occurrence."

The Brigham and Women's Hospital-based Nurses' Health Study has followed the health of female registered nurses since 1976, and the Health Professionals Follow-up Study, based at Harvard School of Public Health, has followed males from several health professions since 1986. These studies recorded height, weight and physical activity for each person enrolled, as well as diet, medications, smoking habits and other health behaviors, and has updated that information every two to four years. Of the 136,623 participants who qualified for their study protocol, Birmann and her colleagues confirmed 215 cases of multiple myeloma.

Body Mass Index (BMI) is computed by dividing a person's weight by the square of their height. A BMI between 18.5 and 25 is considered optimal, a BMI of 25-29 is considered overweight, and a BMI of 30 or higher is considered obese.

The association between BMI and multiple myeloma was strongest among men with a BMI of 30 or more. When compared with leaner men (those with a BMI below 22), obese men, the researchers said, were over twice as likely to develop multiple myeloma. The effect was less pronounced among overweight or obese women, yet those women also had an increased risk.

The study also looked at whether regular exercise is related to risk of multiple myeloma. There was not a clear effect of exercise on risk, although the results among women suggested that those who exercise more might have a lower risk. "We cannot say with certainty that exercise reduces the risk of multiple myeloma, but there is ample evidence that regular exercise offers many other health benefits," Birmann said.

The study findings do show, however, that the effect of BMI on risk of multiple myeloma is separate from any possible effect of physical activity.

According to Birmann, previous research has identified possible biological links between obesity and multiple myeloma. For example, adipocytes, cells found in fat tissue, produce a cell signal, called interleukin-6 (IL-6), which promotes the immune system's inflammation response. In obese people, this can cause an overproduction of IL-6, which in turn creates a cellular environment that sustains multiple myeloma. "The IL-6 chemical pathway is one possible way obesity could influence the risk of developing diseases like cancer or cardiovascular disease, but the answer might also lie in other relationships between obesity and cancer," Birmann said.

Further research, she said, will uncover more about the relationships between obesity and cancers such as multiple myeloma. The researchers believe their findings may lead to examination in greater detail of the BMI/multiple myeloma link, including the role of IL-6 and other chemical signals, energy metabolism, and other risk factors such as weight change or weight cycling.

This research was funded through grants from the Dana-Farber/Harvard Cancer Center Specialized Program in Research Excellence in Multiple Myeloma, the National Cancer Institute and the National Institutes of Health.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Nominations Open for 2008 Landon-AACR Prizes

registration@aacr.org () — Tue, 10 Jul 2007 12:00:00 GMT

PHILADELPHIA - The American Association for Cancer Research is pleased to invite nominations for the seventh annual Landon-AACR Prizes for Basic and Translational Cancer Research. Nominations will be open until August 24, 2007.

These two major international prizes recognize seminal basic and translational cancer research discoveries at the cutting edge of scientific novelty and significance. Eligible candidates are active, recently published scientists who have made extraordinary advances in cancer research, and whose scientific innovation and creativity have accelerated progress against cancer and have implications for future discoveries and contributions to cancer research.

Past winners of the Kirk A. Landon-AACR Prize for Basic Cancer Research:

2007: Richard D. Kolodner, Ph.D.
University of California, San Diego

2006: Robert A. Weinberg, Ph.D.
Whitehead Institute for Biomedical Research, Cambridge, Mass.

2005: Elizabeth H. Blackburn, Ph.D.
University of California, San Francisco

2004: Tony Hunter, Ph.D.
The Salk Institute for Biological Studies, La Jolla, Calif.

2003: Charles J. Sherr, M.D., Ph.D.
St. Jude Children's Research Hospital, Memphis, Tenn.

2002: Robert N. Eisenman, Ph.D.
Fred Hutchinson Cancer Research Center, Seattle, Wash.

Past winners of the Dorothy P. Landon-AACR Prize for Translational Cancer Research:

2007: Douglas R. Lowy, M.D. & John T. Schiller, Ph.D.
National Cancer Institute, Bethesda, Md.

2006: Angela M. Hartley Brodie, Ph.D.
University of Maryland School of Medicine, Baltimore

2005: Janet D. Rowley, M.D.
University of Chicago Medical Center, Chicago, Ill.

2004: Raymond N. DuBois, M.D., Ph.D.
Vanderbilt-Ingram Cancer Center, Nashville, Tenn.

2003: Dennis J. Slamon, M.D., Ph.D.
University of California, Los Angeles Jonsson Cancer Center

2002: Elwood V. Jensen, Ph.D.
University of Cincinnati, Cincinnati, Ohio
and
V. Craig Jordan, Ph.D.
Fox Chase Cancer Center, Philadelphia, Pa.

The recipient of each prize will receive an unrestricted cash award of $100,000. Both will present lectures during the AACR Annual Meeting, April 12-16, 2008, in San Diego, Calif., to stimulate and inspire their colleagues to new thinking and fresh approaches in both basic and translational cancer research. They will also participate in the annual Landon-AACR Prize Symposium at the University of Miami/Sylvester Comprehensive Cancer Center in January 2009.

For further information on the nomination process and other details about the prizes, please click here. Inquiries regarding this award should be directed to Monique Eversley at eversley@aacr.org.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

The Kirk A. and Dorothy P. Landon Foundation was created through a bequest from Mrs. Dorothy P. Landon whose intent, along with that of her late husband, Kirk A. Landon, was to dedicate a major portion of their estate to medical research, especially research related to cancer. Mr. R. Kirk Landon, son of Kirk A. Landon, serves as the President of the Foundation. The Foundation seeks to accomplish its cancer research mission through a variety of programs and initiatives, the most important of which are the Landon-AACR Prizes.

Study Finds Western-Style “Meat-Sweet” Diet Increases Risk of Breast Cancer in Postmenopausal Women

registration@aacr.org () — Tue, 10 Jul 2007 12:00:00 GMT

PHILADELPHIA - A new study finds that the more "western" the diet -- marked by red meat, starches and sweets -- the greater the risk for breast cancer among postmenopausal Chinese women. According to researchers who conducted the analysis at Fox Chase Cancer Center in Philadelphia, Harvard University, Shanghai Cancer Institute, and Vanderbilt University, the findings mark the first time a specific association between a western diet and breast cancer has been identified in Asian women.

The study, published in the July issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, is the latest set of findings derived from the Shanghai Breast Cancer Study, conducted in the 1990s by Wei Zheng, M.D., Ph.D., M.P.H, and colleagues at Vanderbilt University. The Fox Chase researchers identified dietary habits among women in the study based on their reported eating habits, classifying them as either "meat-sweet" or "vegetable-soy" eaters.

"The Shanghai data gave us a unique look at a population of Chinese women who were beginning to adopt more western-style eating habits," said, Marilyn Tseng, Ph.D. associate member in the population science division at Fox Chase. "We found an association between a western-style diet and breast cancer was pronounced in postmenopausal women, especially heavier women with estrogen receptor-positive tumors."

Breast cancers marked by the excessive production of estrogen receptors (ER+ breast cancers) form the majority of breast cancers and are often associated with obesity. According to Tseng, there seems to be a specific interaction between obesity and western cuisine among postmenopausal women that drives breast cancer, although the study did not offer a specific mechanism.

Tseng and her colleagues examined cases of women from the Shanghai Breast Cancer Study, 25 to 64 years of age, who were newly diagnosed with breast cancer from August 1996 to March 1998. Controls were selected from the Shanghai Resident Registry of permanent residents in urban Shanghai.

Through in-person interviews with the Shanghai study participants and residents of Shanghai, researchers established the existence of two primary dietary patterns - a "meat-sweet" diet and a "vegetable-soy" diet. The "meat-sweet" diet is characterized by various meats, primarily pork but also poultry, organ meats, beef and lamb, and shrimp, saltwater fish, and shellfish, as well as candy, dessert, bread, and milk. The "vegetable-soy" pattern is associated with various vegetables, soy-based products, and freshwater fish.

Of 1,602 breast cancer cases identified during the study period, in-person interviews were completed for 1,459 (91.1%). In-person interviews were completed for 1,556 (90.3%) of the 1,724 control group participants.

The "meat-sweet" pattern was significantly associated with increased risk of breast cancer among overweight postmenopausal women. Specifically, high intake of the "meat-sweet" pattern was associated with a greater than twofold increased risk of ER+ breast cancer among these women. The results showed no overall association of breast cancer risk with the "vegetable-soy" pattern.

"Our study suggests the possibility that the "meat-sweet" pattern interacts with obesity to increase breast cancer risk," Tseng said. "Low consumption of a western dietary pattern plus successful weight control may protect against breast cancer in a traditionally low-risk Asian population that is poised to more broadly adopt foods characteristic of western societies."

This research was funded through grants from the National Institutes of Health, the American Cancer Society, and the Commonwealth of Pennsylvania.

Tseng's co-authors include Xiaohui Cui from the Department of Epidemiology of the Harvard School of Public Health, Yu-Tang Gao from the Shanghai Cancer Institute, and Qi Dai, Xiao-Ou Shu, and Wei Zheng from the School of Medicine, and the Vanderbilt-Ingram Cancer Center at Vanderbilt University.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

Skin Rash Actually Signifies Better Outcomes for Pancreatic and Lung Cancer Patients

registration@aacr.org () — Tue, 03 Jul 2007 12:00:00 GMT

PHILADELPHIA - The appearance of a rash in cancer patients treated with erlotinib (Tarceva) is strongly associated with longer survival, according to researchers from the drug's developer, OSI Pharmaceuticals, Inc. This is not the first time that rash has been associated with a survival advantage with EGFR inhibitors - a class of drugs which includes erlotinib, cetuximab, panitumumab and others designed to block overproduction of the epidermal growth factor receptor - but it is the most detailed analysis to date.

The study, published in the July 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, reports that for patients taking Tarceva who developed a moderate to severe rash, survival without progression of disease was 245 percent longer than in patients who had a mild rash or none at all. In fact, in the majority of cases, the more severe the rash, the longer a patient's cancer was held in check, researchers found.

This rash, which often looks like acne, can be unpleasant enough for some people to consider discontinuing treatment, but "it is important for physicians and patients to understand that this a positive event because it means there is likely to be a better clinical outcome," said the lead author, Bret Wacker, MS Director of Biostatistics at OSI Pharmaceuticals, Inc. "Further studies are needed to both identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy."

Although few patients dropped out of the large Phase III clinical trials testing Tarceva in advanced non-small cell lung cancer and pancreatic cancer due to the rash, Wacker said he fears those who are taking Tarceva outside of a clinical trial may be likely to stop treatment.

"Some patients are stopping treatment because of the rash, yet those are the ones who are most likely to benefit," Wacker said. "This is a critical problem and rather than permanently discontinue treatment, patients should talk to their doctor about an effective and proactive strategy to manage the rash while continuing Tarceva therapy."

According to the researchers, these rashes can be controlled with mild steroids or antibiotics, and in most cases, they will improve with treatment. They are believed to be due to an inflammatory response as a result of EGFR inhibition in skin tissue, Wacker said.

The analysis looked at two placebo-controlled, double-blind, randomized, Phase III clinical trials testing Tarceva in advanced non-small cell lung cancer and pancreatic cancer - studies which led to approval of the agent for treating both cancers. Wacker and his team excluded patients who died in the first month after starting the study because they may not have had time to develop the rash or the rash may have been under-reported in these ill patients.

Of the 673 patients in the lung cancer study, called BR.21, and in the Tarceva-treated group, 81 percent developed a rash, the majority of which was grade 2 (The study graded rashes from 1, relatively mild, to 4, severe). The researchers found that the presence of any rash correlated with overall and progression-free survival and that these correlations increased with the grade of rash. Specifically, Tarceva-treated patients who did not develop a rash survived a median of 3.3 months, compared to 7.1 months for those with a grade 1 rash, and 11.1 months for patients with more severe, grade 2 rashes.

They also found, however, that 18 percent of patients treated with a placebo also developed a rash, and that overall survival in these patients was also significantly longer (a median of 8.2 months compared to 4.7 months), compared to placebo patients who didn't develop a rash. "We don't know why some patients treated with a placebo developed a rash, but it could be due to the strength of their immune system, and that is why they survived longer," Wacker said.

In the second clinical trial (known as PA.3) that tested Tarceva and the chemotherapy drug gemcitabine against a placebo drug and gemcitabine in 521 patients with advanced pancreatic cancer, 71 percent of patients using Tarceva/gemcitabine developed a rash, compared with 30 percent of patients in the placebo group.

This increased rate of rashes in the placebo group makes some sense, Wacker said, because rashes are known to occur with use of gemcitabine chemotherapy. But, unlike the BR.21 study, these pancreatic cancer patients with rashes in the placebo group did not experience an increase in survival compared to placebo group patients without a rash.

In the Tarceva treatment group, only a more severe rash of grade 2 or higher was associated with increased survival. Patients with a grade 2 rash survived a median of 10.8 months, compared to treated patients with no rash (5.4 months) or a grade 1 rash (5.7 months). "These different results may be associated with the addition of gemcitabine with Tarceva, or the lower dose of Tarceva in this study, but we just don't know," he said.

Wacker points out that lack of a rash doesn't necessarily mean that patients will not benefit from Tarceva. "A small percentage of patients who didn't develop a rash still had relatively long survival," he said. "But, still, overall, patients who don't develop a rash don't do as well as those who do."

The study was funded by OSI Pharmaceuticals, Inc.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Media Contact:

Greg Lester
(267) 646-0554
lester@aacr.org

Fat Kills Cancer: Turning Stem Cells Taken from Fat Tissue into Personalized, Cancer-Targeted Therapeutics

registration@aacr.org () — Tue, 03 Jul 2007 12:00:00 GMT

PHILADELPHIA - Researchers in Slovakia have been able to derive mesenchymal stem cells from human adipose, or fat, tissue and engineer them into "suicide genes" that seek out and destroy tumors like tiny homing missiles. This gene therapy approach is a novel way to attack small tumor metastases that evade current detection techniques and treatments, the researchers conclude in the July 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

"These fat-derived stem cells could be exploited for personalized cell-based therapeutics," said the study's lead investigator, Cestmir Altaner, Ph.D., D.Sc., an associate professor in the Cancer Research Institute of the Slovak Academy of Sciences in Bratislava. "Nearly everyone has some fat tissue they can spare, and this tissue could be a source of cells for cancer treatment that can be adapted into specific vehicles for drug transport."

Mesenchymal stem cells help repair damaged tissue and organs by renewing injured cells. They are also found in the mass of normal cells that mix with cancer cells to make up a solid tumor. Researchers believe mesenchymal stem cells "see" a tumor as a damaged organ and migrate to it, and so might be utilized as a "vehicle" for treatment that can find both primary tumors and small metastases. These stem cells also have some plasticity, which means they can be converted by the micro environment of a given tissue into specialized cells, Altaner says.

After extracting the stem cells from human fat tissue the researchers worked to find a less toxic way to treat colon cancer than the standard-of-care chemotherapy agent, 5-fluorouracil (5-FU), which can produce toxic side effects in normal cells. They expanded the number of mesenchymal stem cells in the laboratory and then used a retrovirus vector to insert the gene cytosine deaminase into the cell. This gene can convert a less toxic drug, 5-fluorocytosine (5-FC), to 5-FU inside the stem cells, and the chemotherapy can then seep out into the tumor, producing a lethal by-stander effect.

In nude mice - animals with an inhibited immune system - engrafted with human colon cancer, the researchers first injected the engineered mesenchymal stem cells, then 5-FC. They found tumor growth was inhibited by up to 68.5 percent in the animals, and none of the mice exhibited any signs of toxic side effects.

However, none of the animals remained tumor-free. "The procedure was quite effective even though we applied the stem cells just once. Obviously, repeated treatment will increase the efficacy, as would using this strategy in combination with other treatments," Altaner said.

Normal mesenchymal cells can be isolated from various sources, including bone marrow, but the yield is not nearly as great as what the researchers derived from fat tissue. Removal of fat tissue during surgery to remove a tumor would be simple, says Altaner. Liposuction could also be used to isolate mesenchymal stem cells can also be gathered and isolated through liposuction, and the cells frozen in liquid nitrogen for future therapeutic use. Both processes would be easier than taking bone marrow from a patient, Altaner said.

The study was funded by grants from the Slovak Academy of Sciences and the League Against Cancer, and support from the Slovakian national cancer genomics program.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Media Contact:

Greg Lester
(267) 646-0554
lester@aacr.org

From Clinical Cancer Research: Rethinking Therapeutic Cancer Vaccine Trials

registration@aacr.org () — Tue, 03 Jul 2007 12:00:00 GMT

PHILADELPHIA -- Ongoing therapeutic cancer vaccine trials have yet to show evidence of vaccines spurring a patient's immune system to shrink tumors -- yet patients who receive these vaccines in trials tend to live longer and respond better to subsequent treatment. In the July 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, a team of National Cancer Institute researchers asks a fundamental question: are we looking at cancer vaccine trials the wrong way?

"Cancer Vaccines: Moving Beyond Current Paradigms," Jeffrey Schlom, et. al., Clinical Cancer Research, July 1, 2007, Volume 13, No. 13, pages 3776-3782.

In a review of five prostate cancer vaccine trials, NCI researchers offer evidence that patients who receive vaccines may respond better to subsequent chemotherapy or hormone treatment. The specific results - or endpoints - of these clinical trials, however, were not the long term survival of patients, but rather the degree to which the vaccine caused tumors to shrink. According to the researchers, since they didn't achieve their primary endpoints, these vaccines may be abandoned as dead-ends, despite their real therapeutic value in terms of prolonging patient survival.

"Clinical data are providing evidence that patients are living longer following vaccination, despite the fact that trials do not show the vaccines can induce the immune system into shrinking tumors," said Jeffrey Schlom, Ph.D., chief of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute. "The data suggests that the scientific community and regulatory committees ought to rethink the design of clinical vaccine trials and our current approach to measuring the effectiveness of a cancer vaccine."

According to the researchers, it may be more helpful to think of the effectiveness of a vaccine in terms of the response of the patient, rather than the response of the tumor. While the Response Criteria in Solid Tumors (RECIST) experimental standards works well in evaluating therapies that are toxic to tumors, such as radiation or chemotherapy, they are less capable of measuring the more subtle systemic effects of immune response, Schlom said.

While there is no conclusive evidence to explain why a vaccine may lead to better patient survival, Schlom believes the evidence suggests that vaccines are, in fact, priming the immune system. "Vaccines are not passive, they induce a dynamic process of immune response that, in many cases may keep the tumor in check and enhance the effectiveness of subsequent therapies," Schlom said.

About Therapeutic Cancer Vaccines

Unlike preventative vaccines, like those that protect against human papillomavirus or the flu, therapeutic cancer vaccines are given in the hopes of treating an existing disease. These cancer vaccines generally fall into two categories: cell-based, where vaccines are created using cells from the patient's own immune system that have been activated to the presence of cancer antigens and delivered back to the patient along with additional proteins that facilitate immune activation; and vector-based, where an engineered virus, or vector, is used to introduce cancer proteins and other molecules to stimulate the immune system. Both approaches are designed to rile the patient's immune system into attacking tumor cells.

In their review Schlom and his colleagues looked at two cell-based vaccines, Sipuleucel-T (Provenge) and GVAX, as well as three trials using an engineered pox-virus vector. While this review article focuses on prostate cancer vaccines, the researchers consider these trials as examples of ongoing progress in similar vaccine therapies for lymphoma, melanoma, pancreatic, lung and other types of cancer.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Media Contact:

Greg Lester
(267) 646-0554
lester@aacr.org

Gene Variations Directly Link Inflammation to an Increased Risk for Lung Cancer

registration@aacr.org () — Tue, 03 Jul 2007 12:00:00 GMT

PHILADELPHIA- Variations in two genes related to inflammation may be a major risk factor for developing lung cancer, according to a team of scientists from the National Cancer Institute and the University of Texas M. D. Anderson Cancer Center. The effect of these genes is especially strong among heavy smokers, suggesting that the inflammatory response is important in modulating the damage caused by tobacco smoke.

Their study, published in the July 1 issue of Cancer Research, a publication of the American Association for Cancer Research, is the first to pinpoint the mechanism by which damage to the lung might trigger an overzealous inflammatory response by the immune system, leading to lung cancer. The variants, or polymorphisms, were found in genes for interleukin 1A and interleukin 1B, two signaling molecules that immune system cells secrete in response to infection or tissue damage.

"Our findings help explain how heavy smoking, for example, combines with a genetic predisposition to create a besieged environment within the lungs," said lead author Eric Engels, M.D., MPH, researcher at the Viral Epidemiology Branch of the NCI's Division of Cancer Epidemiology and Genetics. "Essentially, sustained inflammation alters the microenvironment of the lung tissue, damaging cells and altering DNA."

Inflammation is part of the immune system's arsenal to combat the effects of infection and cell damage. However, prolonged or intense inflammation could lead to conditions within the lung environment that foster cancer, Engels said. Previous studies have shown that diseases associated with lung damage, such as tuberculosis and asthma, increase the risk of developing lung cancer. Likewise, exposure to tissue-damaging substances like silica and asbestos, inhaled into the lungs, has also been shown to increases lung cancer risk.

"Inflammation has long been thought to be a factor in many cancers, including lung cancer, and could provide an explanation how damage to lung tissue leads to cancer," Engels said. "Knowing more about the downstream effects of these polymorphisms, and discovering others like them, will increase our understanding of how some people are predisposed to developing cancer."

To examine the relationship between inflammation and lung cancer risk, the researchers compared differences in genes related to inflammation between more than 1,500 lung cancer patients and 1,700 controls at M. D. Anderson Cancer Center in Houston, Texas. More than 80 percent of the cancer patients in the study were current or former smokers. Among the 59 variations in 37 inflammation-related genes studied, the researchers discovered that some variants in the genes for interleukin (IL) 1A and 1B, are found more frequently in patients with lung cancer -- and especially among heavy smokers. The effect was most profound in polymorphisms in IL1B, which is central to the inflammation process, the researchers said.

According to Engels, the IL1B protein is an integral part of the chemical cascade by which cell signals moderate the response to inflammation. Variations in the gene may lead to greater expression of the protein, which is more likely to turn on the cascade and sustain the damaging effects of inflammation. Over time, the constant damage of inflammation could lead to genetic damage and cancer, Engels said.

The researchers believe their findings will provide the basis for further lung cancer research as well as a model for examining the nature of inflammation in other types of cancer.

"While smoking is still the greatest risk factor, we still do not understand how other factors play a role," Engels said. "A better understanding of the risks involving inflammation will lead to a better understanding of cancer prevention."

###

Media Contact:

Greg Lester

(267) 646-0554

lester@aacr.org

Researchers Discover Method for Identifying How Cancer Evades the Immune System

registration@aacr.org () — Mon, 02 Jul 2007 12:00:00 GMT

PHILADELPHIA- One of the fundamental traits of a tumor - how it avoids the immune system - might become its greatest vulnerability, according to researchers from the University of Southern California. Their findings, demonstrated in human breast and colorectal cancers, indicate that a technique for determining a tumor's "immune signature," could be useful for diagnosing and treating specific cancers.

In the July 1 issue of Clinical Cancer Research, a publication of the American Association for Cancer Research, the researchers describe a means for determining which genes have been altered in a tumor to allow it to evade the body's natural defenses. In time, the researchers believe such analysis could become a standard practice in cancer diagnosis and treatment.

"The implication is that once you know the mechanism by which tumors evade the immune system, you can match that tumor to available therapies," said senior author Alan L. Epstein, M.D., Ph.D., professor of Pathology at USC's Keck School of Medicine. "First, we find the genetic changes that allow a tumor to defeat the immune system, then we can apply therapies that compensate for these genetic alterations."

According to Epstein, tumors are notorious for demonstrating a broad array of genetic and biological variations. Their differences vary widely between cancer types, even between subcategories within a particular type of cancer. However, while the genetic variations that comprise an immune signature are complex, the researchers discovered that a small subset of genes is integral in explaining immunological behavior.

Using real-time PCR (rtPCR), a high-speed gene amplification technique, Epstein and his M.D./ Ph.D. student, Rebecca Sadun, screened tumors to identify 14 pro-immunity genes, which tumors downplay, and 11 key anti-immunity genes, which tumors promote. They studied the expression of these genes in five mouse tumor models for breast cancer, leukemia, colon cancer, lung cancer and renal cell carcinoma. They then compared two of these immune signatures with corresponding human tumors, eight cases of human ductal carcinoma and 11 cases of colorectal cancer.

Remarkably, the researchers found that the immune signatures of each of the human breast cancer cases nearly matched that of mice. In all cases, the researchers saw a suppression of CD83 and CD28, two genes that affect activation of immune cells, and over-production of B7-H4, a gene whose protein product inhibits immune activation. The human colorectal cancers, however, showed variations in their immune signatures, which researchers saw as an indication of the need to understand the signature for each patient's individual cancer.

"I see it as the beginning stages of personalized medicine, where we develop tactics for treating the unique genetic make-up of a specific tumor," Epstein said. "It becomes even more necessary when we look at all the immunotherapies that are becoming available or are beginning to emerge from research."

In time, Epstein believes, it will be possible to study the immune signatures for most, if not all, forms of cancer. In addition, rtPCR technology allows for a relatively inexpensive and rapid analysis on equipment available at most medical centers, researchers said. "For now, we need to better understand the immune signatures for the most common human cancers in order to identify the most important targets for immunotherapy," Epstein said.

The study was funded by the Philip Morris External Research program by Philip Morris USA, Inc., Philip Morris International and by support provided by Cancer Therapeutics Laboratories, Inc.

###

Media Contact:

Greg Lester

(267) 646-0554

lester@aacr.org

Study Finds that Dietary Vitamin B6, B12 and Folate, May Decrease Pancreatic Cancer Risk among Lean People

registration@aacr.org () — Fri, 01 Jun 2007 12:00:00 GMT

PHILADELPHIA - Researchers exploring the notion that certain nutrients might protect against pancreatic cancer found that lean individuals who got most of these nutrients from food were protected against developing cancer. The study also suggests this protective effect does not hold true if the nutrients come from vitamin supplements.

In a study published in the June 1 issue of Cancer Research, a journal of the American Association for Cancer Research, investigators combined data from four large studies and found that people who were at or below normal body weight decreased their risk for developing pancreatic cancer if they took in high levels of vitamin B6, vitamin B12, and folate from food. The study determined that their risk was 81 percent, 73 percent, and 59 percent lower, vitamin B6, vitamin B12, and folate respectively, compared with participants who did not eat as much of these nutrients or who weighed more. According to the researchers, that was the only statistically significant finding from the study, which is the largest yet to look at these nutrients and pancreatic cancer risk.

"All we can say is that a person who has reason to be concerned about their risk of developing this cancer, which is relatively rare but quite deadly, should maintain a normal weight and eat their fruit and vegetables," said the study's lead investigator, Eva Schernhammer, M.D., Dr.P.H., an assistant professor of medicine at Harvard Medical School.

The researchers also say that they uncovered another interesting trend - that some people who received these nutrients from multivitamin pills had an increased risk of developing the disease. According to the researchers, individuals who said they used multivitamins, and whose blood showed traces of these nutrients, had a 139 percent increased relative risk of developing pancreatic cancer.

"This is a preliminary, but intriguing, finding because it suggests that something in the vitamins may fuel pancreatic cancer growth," Dr. Schernhammer said.

This isn't the first study to suggest that folate, and vitamin B6 and B12 - so called one carbon nutrients - are protective against pancreatic cancer if they come from food, but not if they come from multivitamins, Dr. Schernhammer said.

One large Finnish study found one carbon food nutrients were associated with a decreased risk of developing pancreatic cancer, but that vitamin pills were not helpful. Two other large American studies also found the food nutrients to be protective, but that vitamin use was associated with a higher, yet non-significant risk of developing the cancer.

In this study, researchers combined four large prospective cohort studies, The Women's Health Initiative, and three from the Harvard School of Public Health: the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physician's Health Study. From this large database, they performed a prospective nested case-control study to examine plasma concentrations of the nutrients from participants who had donated blood and answered questionnaires about their food intake and vitamin use before any cancer developed. Their analysis included 208 pancreatic cancer cases and 623 cancer-free control cases.

No one knows why vitamin pills may not help ward off cancer, or why, in this study, it might have a deleterious effect, Dr. Schernhammer said, but some research in animals suggests that "if there is a dormant tumor, folate and other similar vitamins may stimulate growth." That might be especially true if a person did not take in enough of these nutrients consistently through diet, and then suddenly started taking multivitamins in an effort to become healthy, she said.

"People think that dietary intake of these nutrients reflects a lifelong healthy eating habit, and in those cases, these nutrients may be protective, but they could have an opposite effect if they are used in a person with an occult cancer," Dr. Schernhammer said. "It might all depend on whether a person is cancer-free at the time they start using these nutrients."

The same kind of association has been found with use of soy, which is an estrogen-rich food, she said. "Women who have eaten soy all their lives, such as people in Asia, have a reduced risk of developing breast cancer, but some studies have found that increased soy intake in women who have not eaten it before appears to be harmful."

The researchers say their study cannot definitively say that one carbon nutrients either pose a benefit or a hazard to most people, but they note that it is the best analysis that can be performed outside of a randomized clinical trial

The study was funded by the National Institutes of Health.

###

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Quit Smoking Long before Father’s Day: Cigarette Smoke Alters DNA in Sperm, Genetic Damage Could Pass to Offspring

registration@aacr.org () — Fri, 01 Jun 2007 12:00:00 GMT

PHILADELPHIA - The science has long been clear that smoking causes cancer, but new research shows that children could inherit genetic damage from a father who smokes.

Canadian researchers have demonstrated in mice that smoking can cause changes in the DNA sequence of sperm cells, alterations that could potentially be inherited by offspring. The results of their study are published in the June 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

"Here we are looking at male germline mutations, which are mutations in the DNA of sperm. If inherited, these mutations persist as irreversible changes in the genetic composition of off-spring." said Carole Yauk, Ph.D., lead author of the study and research scientist in the Mutagenesis Section of Health Canada's Environmental and Occupational Toxicology Division. "We have known that mothers who smoke can harm their fetuses, and here we show evidence that fathers can potentially damage offspring long before they may even meet their future mate."

Males, whether they are mouse or man, generate a constant supply of new sperm from self-renewing spermatogonial stem cells. Yauk, along with colleagues at Health Canada and McMaster University, studied the spermatogonial stem cells of mature mice that had been exposed to cigarette smoke for either six or 12 weeks to look for alterations in a specific stretch of repeated portions of DNA, called Ms6-hm, which does not contain any known genes. The "smoking" mice were exposed to two cigarettes per day, the equivalent - based on blood levels of tobacco by-products - of an average human smoker, according to research previously published by one of the study's co-authors.

Yauk and her colleagues found that the rate of Ms6-hm mutations in the smoking mice were 1.4 times higher than that of non-smoking mice at six weeks, and 1.7 times that of non-smoking mice at 12 weeks. "This suggests that damage is related to the duration of exposure, so the longer you smoke the more mutations accumulate and the more likely a potential effect may arise in the offspring," Yauk said.

According to Yauk, previous studies have shown that Ms6-hm and similar locations of non-coding DNA are sensitive to damage from radiation, mutagenic chemicals and intense industrial air particulate pollution. While the researchers did not specifically study the protein-coding regions of DNA where genes reside, Yauk notes that previous studies correlate mutations in non-coding regions with those in coding regions, and that some repetitive regions of DNA (not examined in this study) are associated with genes.

"It stands to reason that mutations could also interfere with genes, but our ongoing research looks to clarify the severity of DNA damage throughout the genome," said Yauk. "So, while some men say they'll quit smoking after their child is born, this represents a good reason to quit well in advance of trying to conceive."

Among the next steps in gaining a better understanding of the germline genetic health consequences of smoking, Yauk and her colleagues plan to study how altered DNA manifests itself in the children and grandchildren of male mice that are exposed to firsthand smoke. They also plan to study the effects of secondhand smoke on male mice as well the possibility that the eggs of females are affected by smoke.

Yauk's colleagues include fellow researchers from Health Canada and Martin Stämpfli, Ph.D., and his laboratory team at McMaster University. Funding for this research was provided by grants from the Canadian Regulatory System for Biotechnology and the Canadian Institutes of Health Research.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Fatalistic Beliefs about Cancer Cause Many to Ignore Cancer Prevention Advice

registration@aacr.org () — Thu, 17 May 2007 12:00:00 GMT

PHILADELPHIA -- If you feel that you are fated for cancer, your belief could turn into a self-fulfilling prophecy. According to a national survey of more than 6,000 U.S. adults published in the May issue of Cancer Epidemiology, Biomarkers & Prevention, a substantial number of American adults hold fatalistic beliefs about cancer and are correspondingly less likely to take basic steps to lower their cancer risk, such as exercising, quitting smoking and eating a healthy diet rich in fruits and vegetables.

The study, which analyzes data from the National Cancer Institute's Health Information National Trends Survey, is the first national survey in almost 20 years to assess Americans' knowledge about and attitudes toward cancer prevention. The findings have implications for cancer education efforts.

"Many Americans seem to feel afraid and helpless in regards to cancer, which may be exacerbated by conflicting news reports and a general lack of education on the causes and prevention of cancer," said Jeff Niederdeppe, Ph.D., professor at the University of Wisconsin, Madison. "They say ‘well, there is nothing much you can do about it' and, as our survey shows, they indeed do nothing about it."

The survey asked respondents if they agreed with three statements about cancer. About 47 percent of those surveyed agreed with the statement that "It seems like almost everything causes cancer," while 27 percent agreed that "There's not much people can do to lower their chances of getting cancer." Moreover, 71.5 percent of American adults agreed that "There are so many recommendations about preventing cancer, it's hard to know which ones to follow."

People who maintained at least one of these three beliefs were less likely than others to exercise weekly and eat five daily servings of fruits and vegetables. People who believed that "it's hard to know" what to do were more likely to smoke. All three beliefs, the researchers say, were associated with lower levels of education.

Despite the ready availability of cancer information, the researchers conclude, there has been little progress in changing the belief that "everything causes cancer" in the last 20 years. According to the researchers, it is unclear whether and to what degree media coverage of cancer influences beliefs. While this study did not specifically address the news media's role in enforcing cancer fatalism, Niederdeppe believes that the constantly changing messages people get from the news are often confusing.

"Cancer is a difficult thing to talk about in the space of a single news story," Niederdeppe said. "Science values repetition, while the media values novelty. Those two concepts naturally butt heads, which can confuse people."

If conflicting news accounts of cancer prevention science are the cause of confusion, Niederdeppe says, educators ought to focus on developing simple, straightforward messages in teaching the general public about what they can do to prevent disease.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

Hair straightening chemicals not linked to breast cancer risk in African-Americans

registration@aacr.org () — Thu, 17 May 2007 12:00:00 GMT

PHILADELPHIA - Chemical "relaxers" used to straighten hair are not associated with an increased risk of developing breast cancer among African-American women, say researchers who followed 48,167 Black Women's Health Study participants.

In the May issue of Cancer Epidemiology, Biomarkers & Prevention, researchers from Boston University and Howard University Cancer Center found no increase in breast cancer risk due to the type of hair relaxer used or the frequency and duration of use. Women who used relaxers seven or more times a year over a 20 year span or longer had the same risk as women who used the chemicals for less than a year, researchers say.

"This is good news," said the study's lead investigator, Lynn Rosenberg, Sc.D., professor of epidemiology at Boston University School of Public Health. "The present study is definitive that hair relaxers don't cause breast cancer, as much as an epidemiologic study can be."

Previous research shows that breast cancer incidence is higher among African-American women age 40 or younger than among Caucasian women of the same age, and this increased risk is not fully explained by known risk factors, such as race and family history. At all ages, African-American women are more likely to die of breast cancer than are Caucasian women. To shed light on these findings and to study potential causes of breast cancer and other serious illnesses that affect black women, the Black Women's Health Study was launched across the United States in 1995. More than 59,000 women completed an initial questionnaire and more than 80 percent have answered follow-up questions every two years since, including questions about use of hair relaxers.

Hair relaxers can enter the body through cuts or lesions in the scalp. These products are not fully monitored by the Food and Drug Administration, and thus could contain potentially harmful compounds, Rosenberg said. Manufacturers of hair relaxers and hair dyes are not required to list all ingredients of their products on the packages, as some may be considered trade secrets, she said.

"Because hair relaxers are more widely used by younger African-American women than they are used by older African-American women, a connection with increased risk of breast cancer in younger women seemed possible," Rosenberg said. "Also, millions of African-American women use hair relaxers, and substances that are used by millions of women over a span of many years should be monitored for safety."

The researchers found that younger women used hair relaxers more than older women did. They also discovered that the majority of women used hair relaxers before age 20 and a third used the chemicals at least seven times a year. But when they examined the association between use of hair relaxers and breast cancer, based on 574 newly diagnosed cases of breast cancer identified during the follow-up period, they found no connection between use of relaxers and breast cancer incidence overall or among the younger women, even if use had been frequent and of long duration.

The study was funded by the National Cancer Institute. Co-authors include Julie Palmer, Sc.D., and Deborah Boggs, M.S., of Boston University School of Public Health, and Lucile Adams-Campbell, Ph.D., of Howard University Cancer Center.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

No Magic Tomato? Study Breaks Link between Lycopene and Prostate Cancer Prevention

registration@aacr.org () — Thu, 17 May 2007 12:00:00 GMT

PHILADELPHIA -- Tomatoes might be nutritious and tasty, but don't count on them to prevent prostate cancer. In the May issue of Cancer Epidemiology, Biomarkers & Prevention, researchers based at the National Cancer Institute and Fred Hutchinson Cancer Research Center report that lycopene, an antioxidant predominately found in tomatoes, does not effectively prevent prostate cancer. In fact, the researchers noted an association between beta-carotene, an antioxidant related to lycopene, and an increased risk for aggressive prostate cancer.

According to the researchers, the study is one of the largest to evaluate the role of blood concentrations of lycopene and other carotenoid antioxidants in preventing prostate cancer. Study data were derived from over 28,000 men enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, an ongoing, randomized National Cancer Institute trial to evaluate cancer screening methods and to investigate early markers of cancer.

"It is disappointing, since lycopene might have offered a simple and inexpensive way to lower prostate cancer risk for men concerned about this common disease," said Ulrike Peters, Ph.D., M.P.H., of the Fred Hutchinson Cancer Research Center. "Unfortunately, this easy answer just does not work."

Previous studies suggested that a diet rich in lycopene protected against prostate cancer, spurring commercial and public interest in the antioxidant. Antioxidants protect against free radicals, highly reactive atoms and molecules that can damage DNA and other important molecules in the cell. Since free radical damage increases with age, there has been a long-held suspicion in the scientific community that free radical damage could increase the risk of prostate cancer, a disease that has been clearly associated with age.

Subsequent studies of the potentially protective role of lycopene have been contradictory or inconclusive, according to Peters. In a 2006 study, she and her colleagues looked at the dietary intake of more than 25 tomato-based foods, also using data from the PLCO trial, and found no overall association between lycopene intake and prostate cancer.

In their current study, the researchers followed over 28,000 men between the ages of 55 and 74, enrolled in the PLCO Trial, with no history of prostate cancer. The men were initially screened through a PSA test and digital rectal exam, and were then followed through routine exams and screenings until first occurrence of prostate cancer, death or the end of the trial in 2001. At the beginning of the trial, the men gave a blood sample and completed a questionnaire related to their health, diet and lifestyle.

The researchers focused on non-Hispanic Caucasian men, as the small number of cases among other ethnic groups was statistically insignificant. They found no significant difference between those who had prostate cancer and those who did not in relation to the concentration of lycopene in their bloodstream. "Our results do not offer support for the benefits of lycopene against prostate cancer," Peters said.

Most surprisingly, says Peters, was the relationship between increased risk of aggressive prostate cancer - defined as disease that has spread beyond the prostate - and beta-carotene, another antioxidant found in many vegetables and commonly used as a dietary supplement.

This unexpected observation "may be due to chance, however beta carotene is already known to increase risk of lung cancer and cardiovascular disease in smokers," Peters said.

"While it would be counter-productive to advise people against eating carrots and leafy vegetables, I would say to be cautious about taking beta carotene supplements, particularly at high doses, and consult a physician," Peters said.

Funding for this study was provided through the National Cancer Institute and the U.S. Department of Health and Human Services.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

American Association for Cancer Research Bestows Centennial Medals for Distinguished Public Service

registration@aacr.org () — Mon, 07 May 2007 12:00:00 GMT

Senators Specter, Inouye, Reps. DeLauro, Myrick Honored

WASHINGTON, D.C. - In commemoration of 100 years of progress in cancer research, the American Association for Cancer Research (AACR), the world's oldest and largest scientific organization dedicated to cancer research will honor several congressional leaders with Centennial Medals for Distinguished Public Service at AACR's Centennial Celebration Dinner on May 8, 2007 in Washington D.C. Sen. Arlen Specter (R-PA), Sen. Daniel Inouye (D-HI), Rep. Rosa DeLauro (D-CT) and Rep. Sue Myrick (R-NC), were chosen for this honor by AACR's Board of Directors in recognition of their significant and sustained contributions in the fight against cancer and their efforts to make cancer research a national priority.

Senator Specter, Pennsylvania's senior senator and a cancer survivor, brings remarkable leadership to the fight against cancer. His personal strength in battling cancer while carrying on his critical duties in the United States Senate is a tribute to his courage and dedication to public service. Specter's past advocacy in support of life-saving medical advances, stem cell research, and legislation to strengthen cancer research, prevention, and treatment truly illustrates progress in cancer research.

Senator Daniel Inouye, who lost his wife of 57 years to cancer just over a year ago, has played an important role in establishing and funding the University of Hawaii's Cancer Research Center. The center, uniquely suited to draw its research from an ethnically diverse population, produces research that sheds new light on how genetic, cultural, dietary and environmental factors influence the incidence of cancer.

During her tenure in Congress, Representative Rosa DeLauro has taken a special interest in health care issues. A survivor of ovarian cancer, DeLauro is a leading voice for cancer research. Her work led to the passage of "Johanna's Law" in the 109th Congress - a law that increases awareness of gynecologic cancers. From her position on the Labor-Health and Human Services-Education Appropriations Subcommittee, DeLauro fights to increase funding for breast and cervical cancer screenings and research.

As a co-chair of the House Cancer Caucus, Representative Sue Myrick has focused much of her work in Congress on advancing cancer-related federal policy and has long been an advocate for community cancer care. Her support and leadership have been vital to ensuring that cancer patients across the country have access to high-quality community-based care.

At 1 p.m. Tuesday, May 8, AACR will hold an event at the Willard Hotel in Washington to commemorate the formation of the organization. On May 7, 1907, eleven laboratory scientists and clinicians met at the Willard to discuss the rapidly emerging field of cancer research, effectively forming the AACR. A plaque with original members' photos and a page from the minutes taken at the 1907 meeting will be installed in the Willard gallery.

Centennial activities will also take AACR members - together with colleagues from Friends of Cancer Research (FOCR) and the Association of American Cancer Institutes (AACI) - to Capitol Hill on May 9, 2007, to educate lawmakers about the importance of cancer research. The AACR, FOCR and AACI delegations hope to educate Congressional leaders from both sides of the aisle on the need for continued support of cancer research and advocate for the necessary resources to continue cancer research progress into the next century and beyond.

# # #

Contact:
Staci Vernick Goldberg
267-646-0616
goldberg@aacr.org

Stem Cells: Discoveries Thrust Cancer-Initiating Stem Cells into a Larger Role in Cancer Biology and Treatment

registration@aacr.org () — Wed, 18 Apr 2007 12:00:00 GMT

LOS ANGELES - Recent discoveries about the role of stem cells in cancer have altered the landscape of cancer research. With each new study, scientists are learning more about cancer-initiating properties of stem cells at organ sites and throughout the body. Increasingly, stem cells are examined as the cause - and potential target of treatment - for many, if not all, cancers. At the 2007 Annual Meeting of the American Association for Cancer Research, researchers present new discoveries about stem cells in leukemia, breast and colon cancer that add to the growing evidence that perhaps cancer is, fundamentally, a stem cell problem.

PTEN and HER2 regulate self-renewal and invasion of human mammary stem cells: Abstract 1287

Two genes associated with aggressive breast cancer are linked to a key property of mammary stem cell function, according to researchers at the University of Michigan. The genes, PTEN and HER2, both are involved in the biochemical pathways that mediate stem cell self-renewal, a defining property of stem cells.

According to the researchers, understanding the pathways that regulate stem cell self-renewal is important in developing therapeutics that target the tumor stem cell pool. These genes might also become targets of interest in the treatment of tumors resistant to the drug Herceptin.

"We now believe that our results show further evidence that breast cancer arises from signaling errors in the biochemical pathways that control mammary stem cell self-renewal" said Hasan Korkaya, D.V.M., Ph.D., a research fellow at the University of Michigan's Comprehensive Cancer Center. "Since only stem cells have the ability to self-renew, deregulation of either PTEN or HER2 expands the stem cell populations with self-renewing ability."

According to Korkaya, cells with deregulated - or increased - self-renewing ability will then initiate and maintain tumors that are resistant to current therapies.

The two genes appear to influence stem cell self-renewal by controlling two different arms of the pathway, says Korkaya. In breast cancer, the loss of PTEN is linked to nearly a quarter of all cases, while the overproduction of HER2 is associated with nearly 40 percent of all cases. Patients with a combined defect of PTEN loss and HER2 amplification represent worse prognosis than either defect alone.

To replicate this clinical phenomenon and study the link between stem cell self-renewal and tumorigenesis, the researchers altered the expression of the two genes in a line of human breast carcinoma cells. In experimental settings, their results confirmed this clinical data that either defect increases stem cell population by three to five times. Furthermore, Korkaya observed an additive effect and an approximate 10-fold increase in stem cell population when they created a cell line with deleted PTEN and HER2 overexpression. Another property of aggressive tumors is metastasis; the team also found that these cells had increased invasive capacity in a matrigel invasion assay.

"In general, tumors are heterogeneous including stem and non-stem cell populations in a given malignancy," Korkaya said. "If the stem cells acquired mutations in their self-renewing pathways, they will then begin reproducing at an accelerated rate, leading to a particularly aggressive form of cancer."

The researchers believe further studies will identify new biomarkers that will enable physicians to clinically screen patients for mammary stem cells and provide specific treatments designed to target these cells.

Local Radiotherapy Might Contribute to Leukemia Risk in Breast Cancer by Recruitment of Hematopoietic Stem Cells: Abstract 5050

Radiation therapy affects not only the cancer mass, but also the surrounding tissues, including the bone marrow. Signals from the cells in the bone marrow damaged by cancer radiotherapy could be involved in the development of secondary acute myeloma by drawing hematopoietic stem cells, the blood-producing cells of the bone marrow, from distant sites into the irradiated bone marrow, according to researchers from the Ontario Cancer Institute. Their findings suggest that local radiotherapy leads to leukemia, even though radiotherapy directly affects only a small fraction of the bone marrow.

While often effective in treating breast cancer, localized radiation therapy increases the risk of developing secondary cancer, which most frequently manifests in the form of acute myeloid leukemia. In breast cancer, less than 10 percent of bone marrow is exposed to radiation therapy, yet a much higher percentage of hematopoietic stem cells could be affected.

To understand this effect, the researchers labeled and tracked the movement of hematopoietic stem cells in an animal model. Following local radiation therapy, they found that more than four times more hematopoietic stem cells accumulated in the irradiated bone marrow, compared to the non-irradiated bone marrow. Through molecular screening, they found that cells in the area were creating an overabundance of three protein signals known to recruit hematopoietic stem cells: SDF1, MMP2 and MMP9.

"Cells within the bone marrow send out these chemical signals as a sort of call for help, which recruits a large number of hematopoietic stem cells into the affected areas, supposedly to replace damaged cells," said Carlo Bastianutto, Ph.D., a scientific associate at the Ontario Cancer Institute. "In effect, this becomes a trap for this specific population of stem cells, drawing them into the bone marrow present in the radiation field and getting them exposed to the following radiation cycles. This story might repeat at every cycle of radiation therapy, therefore increasing the chance of producing a leukemic stem cell."

According to the OCI researchers, the recruiting signal might be stopped by chemical blockers, which was shown to inhibit the signals experimentally. "Conceivably, it could be possible to inhibit these chemical signals, and this could reduce the risk of secondary acute myeloid leukemia, but much more research needs to be done," Bastianutto said.

The researchers believe this model could help prevent acute myeloid leukemia in patients with malignancies other than breast cancer.

Prospective identification of highly tumorigenic colon adenocarcinoma cells enriched for stem-like properties: Abstract 1288

Colon cancer could join the growing list of stem cell-related cancers with the discovery of a population of highly tumorigenic primary human colon tumor cells, according to researchers from Biogen Idec.

"Such stem cells could be responsible for the perpetuation of colon cancer and its relapse following successful therapy," said Peter Chu, Ph.D., researcher at Biogen Idec. "Our goal is to improve cancer survival rates by identifying these cancer stem cells in order to pave the way for therapeutics to prevent the relapse or metastasis of cancer."

To identify potential cancer stem cells, also known as cancer-initiating cells, the researchers screened a population of human colon cancer cells for molecular markers that differentiated some cells from others. They found a certain subset of cells produced an exceptional amount of CD44 cell surface receptor protein, a well-studied protein involved in many forms of cancer.

According to Chu, to be identified as cancer stem cells, they had to be highly tumorigenic, creating new tumors quickly and from very few starting cells; had to be self-renewing, possessing a capacity to regenerate; and they had to produce tumors similar to the tumor of origin. "These CD44-producing cells fit the bill, although there is evidence to believe that CD44 overexpression is not the sole marker for colon cancer stem cells," said Chu.

Chu and his colleagues discovered that as few as 10 cells producing high amounts of CD44 were capable of creating tumors in an animal model. In contrast, other tumor cells were 10 to 50 times less tumorigenic. The fact that they were tumorigenic at all, the researchers say, indicates that CD44 alone is unlikely to be the sole indicator of stem cell-ness among the tumor cell population. However, according to Chu, the discovery that high CD44 producing cells have cancer stem cell properties provides an entry point into further research into cancer-causing stem cells.

BRCA1 regulates human mammary stem cell self-renewal and differentiation: Abstract 5700

Mutations in the well-known breast cancer susceptibility gene BRCA1 have a role in the propagation of aggressive stem cell-driven cancer. The findings, according to researchers at the University of Michigan, offer further evidence that breast cancer treatment strategies require a stronger focus on the stem cells that drive the disease.

"Our lab previously identified the presence of mammary stem cells and, since BRCA1 is such a strong predictor of breast cancer, we were interested in the involvement of the gene in stem cells," said Suling Liu, Ph.D., a researcher at the University of Michigan's Comprehensive Cancer Center. "If mammary stem cells are, indeed, the driving force of breast cancer, then we need to know more about their function if we hope to create more effective therapies."

To investigate the role of the gene in stem cells, the team engineered a lentivirus to carry small interfering RNA segments that, in effect, silence the BRCA1 gene. They then observed how a population of mammary stem cells functioned without the ability to produce BRCA1. When BRCA1 was inhibited, the number of stem cells was increased by 75 percent. These new cells, in turn, produced three times the normal amount of a stem cell marker protein ALDH1.

In an animal model of the disease, the knockdown of the BRCA1 gene increased the number of stem cells, which then propagated in the fatty tissues of the breast.

These studies suggest that loss of BRCA1 function leads to a block in cell differentiation, expanding the stem cell pool. Since BRCA1 also regulates DNA repair, this may then produce genetically unstable stem cells which in turn generate tumors in these women.

According to Liu, the loss of a single BRCA1 gene can lead to stem cell propagation. The researchers believe their findings might lead to better BRCA1 screening in women with a family history of breast cancer.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Cancer Tip: Nanoparticles Can Damage DNA, Increase Cancer Risk

registration@aacr.org () — Tue, 17 Apr 2007 12:00:00 GMT

LOS ANGELES -- Tissue studies indicate that nanoparticles, engineered materials about a billionth of a meter in size, could damage DNA and lead to cancer, according to research presented at the 2007 Annual Meeting of the American Association for Cancer Research.

Nanoparticles are small enough to penetrate cell membranes and defenses, yet they are large enough to cause trouble by interfering with normal cell processes, researchers at the University of Massachusetts say. Such nanoparticles are currently in use in electronics, cosmetics, and chemical manufacturing, among others industries. Because of their extremely small size, they can be difficult to isolate from the larger environment, as they are much too small for removal by conventional filtering techniques.

When nanoparticles find their way into cancer cells, they can wreak havoc, according to Sara Pacheco, an undergraduate researcher at the University of Massachusetts. Yet very little is known about how they behave in the environment or how they interact with and affect humans.

"Unfortunately, only a very small portion of research on nanoparticles is focused on health and safety risks, or on threats to the environment," Pacheco said. "I am concerned because so many new nanoparticles are being developed and there is little regulation on their manufacture, use and disposal."

Pacheco and her colleagues looked at how two different types of nanoparticles could cause DNA damage in the MCF-7 line of breast cancer cells.

She and her team examined the genotoxicity of silica and C60 fullerene nanoparticle suspensions using the alkaline single-cell gel electrophoresis assay (Comet assay) to quantify breaks in single and double stranded DNA. The team chose these particular nanoparticle types because they are commonly used commercially - in electronics, textiles and sporting goods - and easy to work with in the laboratory setting.

"We observed both dose-dependent and time-dependent increases in DNA damage in breast cancer cells exposed to either aqueous colloidal silica or C60 fullerenes," Pacheco said. "The DNA damage could potentially lead to mutations and ultimately increase the risk of cancer."

One problem is that, while it's clear that some nanoparticles can be more toxic than others, there's not enough data as yet to determine the most dangerous types.

"A lot is unknown about nanoparticle function, but clearly both size and composition are important," Pacheco said. "Several studies have shown that smaller particles are more likely to enter cells and cause more toxicity."

According to Pacheco, what makes matters worse is the fact that so far, aside from preventing their release, there are no known ways to prevent the harmful effects of environmental nanoparticles.

"It is important to know whether the nanoparticles are entering the cell and causing DNA damage directly or if they are acting on the membrane and inducing a cascade of events resulting in DNA damage," Pacheco said. "Once we understand the mechanisms by which nanoparticles induce their toxicity, we will be better able to prevent or mitigate their harmful effects."

In the meantime, the experimental team suggests that great caution should be taken in handling such nanoparticle suspensions and that any uncontrolled release should be avoided.

"Until we understand which types of nanoparticles are harmless and which have the potential to be harmful, I think it is prudent to limit their introduction into the environment," recommended Pacheco.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Cancer Vaccines: Taking a Jab at Cancer by Stimulating the Immune System

registration@aacr.org () — Tue, 17 Apr 2007 12:00:00 GMT

LOS ANGELES - As the first FDA-approved cancer vaccine, designed to protect against human papillomavirus, has moved from scientific discussion to social debate, other vaccine studies are continuing to make progress. While HPV vaccine efforts had the "benefit" of a viral source for the disease, other researchers are developing vaccines for cancers that are not virally based, in an effort to coax the immune system into attacking cancerous cells. Today at the 2007 Annual Meeting of the American Association for Cancer Research, presentations on ongoing HPV trials and other new approaches to stimulating the immune system are injecting momentum into cancer vaccine research.

Substantial impact on precancerous lesions and HPV infections through 5.5 years in women vaccinated with the HPV-16/18 L1 VLP AS04 candidate vaccine: Abstract 4900

Ongoing evaluation of a phase II trial of a human papillomavirus vaccine, developed to prevent cervical cancer, shows that the vaccine continues to protect against HPV types 16 and 18 at five and a half years into the study, according to researchers from the University of Louisville. Their findings also show that the vaccine offers significant cross-protection for HPV types 45 and 31.

The study follows 1113 women between the ages of 15 and 25 in North America and Brazil randomized to receive three doses of either the vaccine or the control. The vaccine, made by GlaxoSmithKline, which funded the study, is designed to protect against two strains of HPV, types 16 and 18, which together are thought to cause nearly 72 percent of all cases of cervical cancer.

At over five years into the study's follow-up, the researchers found that approximately 98 percent of subjects still maintained protection against HPV types 16 and 18. Regardless of HPV status, the vaccine also appears to prevent most occurrences of cervical intraepithelial neoplasia lesions - abnormal, precancerous cell growths found in the cervix.

They also found that the vaccination offered significant protection against genetically similar viruses. They determined the vaccine to be 88 percent effective against HPV type 45 and 54 percent effective against HPV type 31.

"Overall, it is not a surprise that the vaccine offers protection against additional types of human papillomavirus, as they are all related genetically," said Stanley Gall, M.D., professor at the University of Louisville. "However, as you get genetically farther from types 16 and 18, you would expect to see less cross-protection."

According to Dr. Gall, effective preventative treatment with the vaccine will depend on the long-term and broad protection the vaccine can offer against cancer-causing HPV types.

High Sustained Efficacy of a Prophylactic Quadrivalent Human Papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) Vaccine against Cervical Intraepithelial Neoplasia (CIN) grades 2/3 and Adenocarcinoma in situ (AIS): Abstract LB-187

Three years following administration of the quadrivalent human papillomavirus vaccine Gardasil, nearly 100 percent of vaccinated women are protected against pre-cancerous lesions caused by HPV types 16 and 18, according to Indiana University School of Medicine researchers. The HPV vaccine study, which encompassed 12,167 women, age 16 to 23, was one of two phase III trials that led to FDA approval of the vaccine, developed and manufactured by Merck & Co., Inc.

"After three years, we see that the vaccine remains highly effective against HPV 16 and 18 -related precancerous cervical and other genital lesions caused by these HPV types," said Darron R. Brown, M.D, Professor of Medicine, Microbiology and Immunology at the Indiana University School of Medicine. "The high degree of efficacy and safety of this vaccine is remarkable."

The "quadrivalent" vaccine was designed to protect against four types of human papillomavirus: types 6 and 11, which cause genital warts, and 16 and 18, which account for nearly 70 percent of all cervical cancers. According to Dr. Brown, HPV 6 and 11, while not oncogenic, were included in the vaccine since they cause genital warts and may also cause abnormal Pap smear results, leading to expensive and sometimes unnecessary follow-up tests and treatments.

The vaccine also proved highly effective against cervical intraepithelial neoplasia grades two and three, precancerous cervical lesions that are frequently caused by type 16 HPV. Brown and his colleagues report only a single woman in the experimental group presented with an early type 16 lesion, whereas 42 women in the placebo group were diagnosed with HPV 16 or 18-related cervical intraepithelial neoplasia grades two or three, or adenocarcimona.

The vaccine works by triggering the patient's immune system to produce antibodies to viral proteins analogous to those produced on the surface of each of the four types of HPV. These antibodies, in turn, should offer lasting protection against subsequent natural infection by any of the four HPV types.

According to Dr. Brown, preliminary laboratory studies have shown that antibodies triggered by the vaccine were also found to neutralize HPV types 31 and 45, oncogenic types related to HPV types 16 and 18. This research, in parallel to the ongoing study, is examining the quadrivalent vaccine's cross-protective effects against the viruses that cause the remaining 30 percent of cervical cancer cases.

Analysis of the immunological response to a MUC-1 loaded DC vaccine for human pancreatic cancer: Abstract 4896

Results from a Phase I study of a pancreatic cancer vaccine may offer clues toward promoting long-term survival from the disease, according to researchers from the University of Pittsburgh Cancer Institute.

The researchers gave a dendritic cell vaccine to 12 pancreatic cancer patients. Four of the subjects have shown no signs of recurrence in the three years since the study began.

"The trial was a look at the toxicity and feasibility of using a dendritic cell-based vaccine against pancreatic cancer," said Andrew Lepisto, Ph.D., post-doctoral researcher in the University of Pittsburgh's Department of Immunology. "While we are unlikely to run large-scale trials with this particular form of the vaccine due to difficulty in its manufacturing, we have learned a tremendous amount from the subjects that benefited from the trial, which may translate well into more practical vaccine formulations."

The dendritic cell vaccination strategy combines a cancer protein with the patient's own dendritic immune cells. These cells are antigen presenting cells that, in effect, advertise the presence of the antigen molecule to the rest of the immune system. The antigen, MUC-1, is a protein that is over-produced by pancreatic cancer cells. By presenting patients with MUC-1 on dendritic cells, the researchers expected that they could influence the white blood cells to attack pancreatic cancer cells.

The study data suggests that the key to the effectiveness of the vaccine could be in controlling the regulatory T cells, which suppress the immune system, says Lepisto. Prior to vaccination, the pancreatic cancer patients had significantly more regulatory T cells than normal, which then increased following each injection. Likewise, the patients also experienced an increase in effector T cells, white blood cells that respond against antigen.

"Our next step is to create a strategy that allows us to downplay the regulatory T cells while still benefiting from the increase of effector T cells," Lepisto said.

Each year, pancreatic cancer kills approximately 32,000 people in the United States alone. Pancreatic cancer is notoriously resistant to conventional cancer therapies and has one of the lowest five year survival rates of all cancers.

Wild type sequence p53 as a vaccination target for squamous cell carcinoma of the head and neck: Abstract 5113

Researchers from the University of Pittsburgh and the Gunma University School of Medicine have developed a vaccine that enlists multiple parts of the immune system into targeting p53 in head and neck squamous cell cancer. A phase I clinical trial of the vaccine is currently underway at the University of Pittsburgh Cancer Institute.

According to researchers, this is the first vaccine that takes a multi-pronged approach to stimulating the immune system with derivatives of wild type - or non-altered - p53, a tumor suppressor gene. Loss of suppressor function or alteration of the p53 gene factors into nearly 80 percent of human tumors. Tumor cells with altered p53 generally tend to accumulate the protein, which led the researchers to create a strategy that would allow the immune system to destroy tumor cells by targeting p53.

"Instead of creating a vaccine based on mutant p53, which would require a custom vaccine for every patient, our strategy is to target parts of the unaltered p53 protein that can best activate the immune system," said Theresa Whiteside, Ph.D., professor at the University of Pittsburgh School of Medicine. "We are using different unaltered portions of the p53 molecule to entice the immune system into attacking tumors."

According to the investigators, their vaccine uses three different p53-derived peptides to elicit responses from different aspects of immune system. The vaccine currently in trial uses autologous (patients' own) dendritic cells (DC) pulsed with a combination of three peptides: two that trigger cytotoxic T cells, which directly kill targeted tumor cells, and one peptide that stimulates helper T cells.

Altogether, it is an approach that not only excites the killer T cells into action, but also influences the helper T cells, which are instrumental in sustaining the killer T-cell response. The combined strategy has already shown great promise in studies using animal models and human cells in culture, according to the researchers.

The phase I trial, which will eventually enroll 24 patients with head and neck cancer, has three experimental arms, each including a DC-based vaccine containing p53-derived T cell-specific peptides. The three groups vary on whether the cytotoxic p53 peptides are delivered alone or in combination with a helper T cell-activating peptide that is either specific to p53 or not specific to p53.

"Despite great medical progress, the survival rate in head and neck cancer still remains very poor, at about 50 percent, and there is a definite need for new treatment modalities like vaccination," Whiteside said. "Targeting of p53, however, is a strategy that could also work in treating a number of different cancer types, since p53 loss of function is such a common feature of many cancers."

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Personalized Medicine: Genes and Biomarkers That Allow Doctors to Choose the Right Therapy for the Right Patient

registration@aacr.org () — Tue, 17 Apr 2007 12:00:00 GMT

LOS ANGELES - Genetic and epigenetic variations ensure that no two people are exactly alike, and the same holds true for any two cancers. Now, researchers have the tools and the knowledge to help predict how individuals will respond to cancer therapies, enabling them to create more effective therapies for individual cancers - personalized medicine. At the 2007 Annual Meeting of the American Association for Cancer Research, researchers present new biomarkers - and techniques for determining biomarkers - that could determine how an individual might respond to drug or radiation therapy.

Molecular predictors of drug response in breast cancer: Abstract 4963

Researchers at Lawrence Berkeley National Laboratory have identified gene expression signatures that could serve as biomarkers to predict how individuals will respond to the breast cancer drugs lapatinib and CI-1040. Their findings could help in individualizing treatments for women, and their methodologies could aid in identifying similar biomarkers for responses to other drugs and for other types of cancer.

"Individuals respond differently to different therapeutics because there are substantial differences in the spectrum of genetic, biological and epigenetic characteristics between breast cancers, although some recurrent abnormality patterns are emerging that define breast cancer subtypes" said Joe W. Gray, Ph.D., staff scientist and director of the Life Sciences Division at Lawrence Berkeley National Laboratory. "We need better ways to identify how we can best tailor existing therapies to individuals and how to target experimental agents."

Gray and his colleagues have developed a system to evaluate drug response comprised of a panel of 50 breast cancer cell lines. Each of these cell lines represents a single variant among the different genomic abnormalities found among breast cancers. They measured molecular profiles of each cell line and used these to identify subsets of cell lines that represent the subtypes observed in analyses of primary tumors.

By correlating the responses of these cells to targeted therapeutic drugs, the researchers were able to identify the molecular characteristics of cells that were most sensitive to the drugs. They tested their approach by analyzing responses of the cell line panel to lapatinib, a duel inhibitor of EGFR and ErbB2 and CI-1040, a MEK enzyme inhibitor. These studies defined molecular signatures that predicted individual responses among the cell lines to the drugs. For Lapatinib, the strongest correlate of response was amplification and over expression of ErBB2, consistent with clinical experience. For CI-1040, changes in the MEK pathway were most strongly associated with response. Predictors based on combinations of molecular correlates of response were able to quantitatively predict individual cell line responses.

"The concordance of our markers of response to lapatinib with those observed clinically suggests that the molecular markers identified in the cell line collection can be used to guide the use and testing of other approved and experimental drugs," Gray said. "This is important since it is logistically and financially impossible to test all of the experimental medicines in each cancer subtype. This ‘systems' approach suggests a way to prioritize drugs for use in patients and for initial clinical tests."

According to Gray, a large number of emerging therapeutic agents should be prioritized for testing in the subtypes of breast cancer along with other cancers and their subtypes. When therapies are ineffective, they may produce harmful side effects and decrease a patient's quality of life.

KRAS mutation in colorectal cancer is a predictive factor of response and progression free survival in patients treated with Cetuximab: Abstract 5671

Mutations in the KRAS oncogene could predict a lack of response to the drug cetuximab in patients with colorectal tumors. For those with the mutations, the drug is likely to be inefficient and possibly harmful, according to researchers at France's Institut National de la Sante et de la Recherche Medicale (INSERM).

"Because a variety of different effective agents may now be available for any given type of cancer, deciding which treatment regimen is likely to be the most effective and the least toxic is more complicated than ever," said Pierre Laurent-Puig, M.D., Ph.D., a professor of Oncology at University of Paris-Decartes. "Characterizing the factors that are predictive of toxicity and efficacy could lead to significant improvement in both the quality of treatment and outcomes."

Cetuximab, an antibody that attacks the ability of cells to respond to the epidermal growth factor, has been previously shown to be effective in treating metastatic colorectal cancer.

Dr. Laurent-Puig and his colleagues studied 114 patients who had been given cetuximab in combination with another drug, irinotecan.

According to the researchers, approximately 30 percent of patients may have a poor response to the drug. Almost none of the patients who responded to the drug had an activating KRAS mutation, as compared to 35 percent of the patients with stable disease or 55 percent of the patients with progressive disease.

According to Dr. Laurent-Puig, this might be due to the cascade of molecular interactions that occur after epidermal growth factor meets its receptor, EGFR. The KRAS enzyme is a key component to these molecular actions, but mutations in the KRAS gene could allow the enzyme to function whether or not it receives the commanding signal from EGFR. Therefore, the inhibition of EGF receptor by cetuximab will not block the molecular signals that are activated farther down the cascade.

The researchers also determined that KRAS mutations are independent of another predictive marker of cetuximab response, skin toxicity, which appears through a variety of forms including rashes, eczema and fissures. Skin toxicity also indicates a poor response to cetuximab. The study indicated that median survival is 15.6 months for patients with skin toxicity and without a KRAS mutation; whereas the survival is only 5.6 months for patients with the mutation, but no skin toxicity.

Dr. Laurent-Puig and colleagues are continuing to investigate the molecular biomarkers associated with cetuximab, including in tumors without the KRAS mutation that do not respond to the drug.

Recombinant peptides as biomarkers for cancer response to tyrosine kinase inhibitors combined with radiation: Abstract 4657

A new method for determining biomarkers could allow physicians to personalize lung or brain cancer therapy and lower the risk of unnecessary radiation treatments. Researchers at Vanderbilt University are using a biomarker library of peptides to determine whether or not tyrosine kinase inhibitor therapy, combined with radiation therapy, is indeed effective against lung or brain cancer.

"It is difficult to assess the response of cancer in the brain or lung to treatment, since those neoplasms are difficult to access safely," said Roberto Diaz, M.D., Ph.D., a resident in Radiation Oncology at the Vanderbilt-Ingram Cancer Center. "With the proper biomarkers physicians may be able to tell if a patient is not responding to the therapy and alter their treatment strategy accordingly."

The researchers screened lung and brain tumors to determine which peptides - or protein fragments - were active in the tissue environment surrounding the tumors. This phage displayed library - called so after the bacteriophage viruses used to capture protein fragments - was then isolated and tested.

With the library, Dr. Diaz and his colleagues could select peptides that bind to tumors that are affected by a combination of radiation and tyrosine kinase inhibitor therapy, but not to tumors that do not respond to therapy. Ultimately, they uncovered 44 peptides that serve as biomarkers for response to therapy. According to Dr. Diaz, the physiological role of the 44 peptides might also point toward new cancer therapies.

"This study provides us with a starting point for understanding how tumors physiologically respond to therapy and a non-invasive technique for monitoring that response," Dr. Diaz said.

Cellular pharmacogenomic to discover genetic determinants of Tykerb response: Abstract 5684

A new high-throughput genetic analysis technique can reveal gene markers - by the dozens - that determine how a patient might respond to certain cancer drugs, according to scientists at the Translational Genomics Research Institute (TGen). The TGen researchers have found 164 genes that are involved in regulating the sensitivity of squamous cell head and neck cancer cells to lapatinib, a cancer drug that was recently approved for use in metastatic breast cancer under the name Tykerb.

The study, a collaboration with GlaxoSmithKline, evaluated 7,000 genetic targets in human head and neck cancer cells to discover specific genes that might shade an individual's response to Tykerb.

"Our goal is to apply advanced cellular genomic strategies to assist clinical drug development by finding gene states that predict a patient's response to a specific drug, and which combination of drugs produce the most favorable response." said Spyro Mousses, Ph.D., director of the Pharmaceutical Genomics Division at TGen. "In this study, we were able to discover new candidate gene states that may be useful in determining a patient's sensitivity or resistance to Tykerb, and the results have revealed several sensitizing drug targets that reveal a set of candidate combination drugs that are predicted to be synergistic with Tykerb."

Tykerb is an enzyme inhibitor that effectively blocks two cell receptors, ERBB2 and EGFR, from receiving molecular signals. By blocking these signals, Tykerb could effectively shut down the growth of solid tumors, such as those found in breast, lung and head and neck cancer. However, molecular mechanisms within the cell, largely determined by genetics, could determine how effective cancer drugs are for a particular recipient, Mousses said.

To search for target genes that regulate Tykerb response, Mousses and his colleagues performed a genome-scale scan of two cancer cell lines using high-throughput RNAi, "interfering" RNA strands that bind to and knock out one gene individually, across the genome. It is a systematic and highly efficient technique that uses high-speed mechanization to quickly evaluate how specific genes might affect the cell's sensitivity to an agent, Tykerb in this case.

The TGen researchers are currently in the process of refining their genetic "hits" and learning more about how cancer specific variations in these sensitizing genes might further affect Tykerb response. While their findings are still at a preliminary stage, Mousses and his colleagues believe their studies will provide important insights into how to predict oncology drug response and much needed genomic intelligence to support commercial drug development.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

AACR, FDA and NCI Announce Cancer Biomarkers Collaborative at the AACR 2007 Annual Meeting

registration@aacr.org () — Tue, 17 Apr 2007 12:00:00 GMT

LOS ANGELES -The American Association for Cancer Research, together with the Food and Drug Administration and National Cancer Institute, today announces the formation of the AACR-FDA-NCI Cancer Biomarkers Collaborative (CBC) to facilitate the use of validated biomarkers in clinical trials and ultimately in evidence-based oncology and cancer medicine.

The Collaborative brings together leaders from academia, government, industry, and patient advocacy groups to develop a set of best practices for effectively integrating predictive biomarkers into clinical trials.

"Major advances in cancer biology over the last quarter century have provided us with a better fundamental understanding of cancer in all of its forms, yet the translation of this knowledge into medical practice remains painstakingly slow," said William N. Hait, M.D., Ph.D., President of the American Association for Cancer Research. "Therefore, we are joining forces with our partners to find new ways of exploring the use of biomarkers in cancer detection and treatment, without sacrificing high standards for safety and efficacy."

"The FDA's Critical Path is an important initiative that aims to modernize the processes and methods used to evaluate the safety, efficacy and quality of medical products as they move from product selection and design to mass manufacture," said Samir Khleif, M.D., of the NCI and Special Assistant to the FDA Commissioner.

The Collaborative evolved from a special "Think Tank" session of academic, industry and government researchers and patient advocacy groups held at AACR's headquarters in Philadelphia in November, 2006. Think Tank participants laid the groundwork for the new collaborative and identified four priority areas of research to focus on: biospecimens, bioinformatics, assay validation, and information sharing.

This summer, the Collaborative will meet again in Philadelphia to discuss various aspects of these four areas as they relate to biomarker validation and to begin to develop best practices for integrating predictive biomarkers into clinical trials.

These best practices will inform the Critical Path Initiative, the FDA's effort to modernize the scientific process through which a potential human drug, biological product, or medical device is transformed from a discovery or "proof of concept" into a medical product.

"We believe that the CBC will address the mission of the AACR, the goals of the NCI, and the FDA's Critical Path Initiative and will make a major contribution to the success of a new generation of clinical trials and to progress in cancer drug development," said James H. Doroshow, M.D., Director of NCI's Division of Cancer Treatment and Diagnosis.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Drug Studies: Gene Therapy, Cancer-Killing Viruses and New Drugs Highlight Novel Approaches to Cancer Treatment

registration@aacr.org () — Tue, 17 Apr 2007 12:00:00 GMT

LOS ANGELES - Studies presented at the 2007 meeting of the American Association for Cancer Research show how researchers are using the new, as well as the natural, to help design and test new drugs to treat cancer.

For example, researchers are marrying the latest technologies and drug design together to figure out if a drug is having a biological impact, what the effect is, when it stops working and what can be done about it. They have "watched" as an experimental angiogenesis inhibitor shrank deadly brain tumors and when it began to fail. By reading blood proteins they discovered why that happened, and how a combination of therapies might work better.

Scientists are also turning to existing "natural" biological systems to help them design next era cancer therapies. Several research groups are making progress in turning viruses into smart search-and-destroy tumor busters that will leave normal cells alone, and others are finding that marijuana's active ingredient can tweak receptors on the most common form of lung cancer and reduce cancer growth.

Eradication of resistant prostate cancer by a novel gene therapy approach: Abstract 4182

A research team at Columbia University has designed a novel viral-based gene therapy they say blasts through a body, targeting both primary and distant tumors, while leaving normal cells untouched. In the 15 mice they tested, injections of the therapy in tumors on one side of the mouse eliminated those cancers as well as tumors on the other side of the animal's body, producing a cure in all of the mice.

This study tested this "dual cancer-specific targeting strategy" with aggressive therapy resistant prostate cancer. The researchers have also shown it works in animals with breast, and melanoma tumors.

An earlier version of the therapy showed powerful effects in a phase I clinical trial, said Paul B. Fisher, M.Ph., Ph.D., professor clinical pathology at Columbia. This improved treatment appears to be a much "smarter bomb with potential of treating metastatic and therapy-resistant cancers," he said.

"The beauty of this approach is that two methods are being used to destroy a tumor," said Devanand Sarkar, M.B.B.S, Ph.D., the study's primary author, associate research scientist at Columbia. "The virus we designed replicates within a tumor, and at the same time produces a massive amount of a cancer killing compound. Either action alone is damaging and potentially deadly, but together they are lethal."

Columbia researchers built the therapy around their earlier, pivotal discovery of a cytokine (a signaling protein) called melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24). A technology developed in the Fisher laboratory, "subtraction hybridization," applied to human melanoma, induced the cancer to revert to a more normal state, allowing comparison of genes expressed in both states. They discovered mda-7/IL-24 was progressively down-regulated as melanoma developed. In its normal state, the cytokine may affect growth and immune regulation, whereas expression at high levels kills cancer cells.

The investigators altered an adenovirus to carry the mda-7/IL-24 into tumors that normally did not express the gene, and based on successful animal studies, this cytokine was tested for safety in patients with advanced melanoma and other solid cancers. "Interestingly, this phase I clinical trial produced a significant clinical response," Fisher said.

To make the treatment more potent, they then paired the mda-7/IL-24 gene with a "replication competent" adenovirus, a virus that can multiply within cells. After such a microbe enters a cell, it can reproduce and cause the cell to burst, releasing more viral particles. During replication, the mda/IL-24 gene is also reproduced and then expressed, delivering huge quantities of active mda/IL-24 locally and systemically.

Finally, the researchers worked out a strategy to ensure that the loaded virus would only replicate within cancer cells. They manipulated the viral genome again, and substituted its normal promoter (E1A) with a promoter (PEG-3) that they discovered could only be activated by transcription factors found in cancer cells. That means that if the virus may enter a normal cell, it won't replicate and the cell will not die, the researchers say. It also suggests that the therapy will work in a variety of cancers "because virtually all cancers we have tested contain the necessary transcription factors that activate the PEG-3 promoter," Fisher said.

When the viral gene therapy was injected into tumors growing in the mice, the virus replicated and produced mda-7/IL-24, which then killed the tumors, releasing millions of newly produced, loaded viral particles throughout the blood circulation to settle into distant tumors where the process was repeated. It also worked on prostate cancer resistant to other therapy because the two-pronged attack "overwhelmed their defense mechanisms," Sarker said.

Although Sarkar and Fisher say the results are exciting, they stress that additional research is needed prior to testing the therapy in humans, including experiment in mice with an intact immune system. While a primary immune system response against the virus may eliminate some of the loaded particles, the researchers say that the mda-7/IL-24 will likely heighten a secondary therapeutic immune response, offering a much stronger cancer-killing potential.

AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients: Abstract 2118

A phase II clinical trial of an angiogenesis inhibitor to treat glioblastoma has shown promise in a majority of patients tested, say researchers at Massachusetts General Hospital and Harvard Medical School. But they also say that the novel imaging and biomarker studies they performed as treatment was underway have revealed why the treatment, AZD2171, ultimately failed, and what might improve the response.

The imaging studies, which used specially adapted Magnetic Resonance Imaging (MRI) scans, exposed a "window" during which the blood system feeding the tumor reverted to a more normal state, before morphing again into the leaky, dilated vessels that make drug treatment difficult.

The blood biomarker studies showed that as tumors stopped relying on vascular endothelial growth factors (VEGF) to pump up blood flow to them - and VEGF is what AZD2171 targets - they started using two other growth factors, neither of which had previously been recognized as important for human tumor blood vessel growth.

The study is unique because it is the first to test AZD2171 in glioblastoma patients, and to find that it "offered promising benefits such as tumor shrinkage and reduction of brain swelling," said Tracy Batchelor, M.D., chief of neuro-oncology at Massachusetts General Hospital.

Of 31 patients who participated, more than half experienced tumor shrinkage of 50 percent or more, and median time to tumor regrowth was 111 days. "This was not a randomized study, but compared to historical benchmarks, in which response to conventional therapies is approximately 10 percent and progression is usually 63 days, these results are encouraging," Dr. Batchelor said.

The agent, which has been tested in other tumor types but is not yet approved, also reduced edema, or swelling, in the brain, he said. Because of that, some patients were able to stop using steroids, which can cause debilitating side effects.

The clinical trial also provided insights into how AZD2171 functions and how the therapy might be improved, the researchers say. MRI scans taken before, during, and after treatment provided a timeline picture of AZD2171's effectiveness, and then loss of function as tumors began to resist the agent.

"This was beautiful," said Rakesh Jain, Ph.D., professor of tumor biology at Harvard Medical School. "We were able to see changes within 24 hours of taking a single dose."

Jain and his colleagues have spent years documenting how developing cancers promote blood growth factor signaling, which causes blood vessel architecture to go seriously awry: vessels loop back on each other, send blood in the wrong direction, and become enlarged as well as leaky due to holes that develop. They have found regions in solid tumors in which blood flows briskly, and others in which there is little or none. "If we try to deliver drugs to those latter areas, they do not arrive," Jain said.

Still, cancer cells are alive in those hypoxic regions, and, in fact, they morph into much more aggressive cells, he said. It is also in these areas where cancer stem cells might hide. "Buried deep in this hostile environment are the cells responsible for invasion and metastasis," Jain said.

The blood biomarker studies allowed them to track what was happening in the tumors. The researchers discovered that as expression of VEGF proteins decreased, levels of two other proteins increased as the tumor switched to other pathways. One of these proteins, fibroblast growth factor (FGF), was thought to be involved in angiogenesis, but the other, chemokine stroma-cell-derived factor 1 alpha (SDF1α), was a new discovery, Jain said. "We threw a net up with the biomarker studies and found the involvement of FGF, which had never been documented in patients, and SDF1α, which was not known to be one of several dozen pro-angiogenic molecules identified so far in such studies."

"We all recognize that what we need to do now is combine this therapy with other types of treatments, either existing or to be developed, and to deliver these drug combinations during the window we have identified," Dr. Batchelor said. "This might help us manage patients much more effectively."

Δ-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer: Abstract 4749

The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.

They say this is the first set of experiments to show that the compound, Δ-9 tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.

THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer.

"The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer," said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.

Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.

In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. "When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays," Preet said.

Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.

Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.

Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. "THC offers some promise, but we have a long way to go before we know what its potential is," she said.

Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas: Abstract 4185

Researchers in Germany have hidden vaccine-grade measles virus inside artificially generated blood cells in order to devise a search-and-destroy therapy for human brain cancer that can't be "seen" by the immune system.

They say their mouse experiments show a proof of principle that this non-pathogenic virus can attack glioma by getting inside tumor cells and replicating, destroying the common brain tumors from the inside out. This and other so-called "oncolytic" viruses are already being tested in clinical trials, but their effectiveness has been limited by an immediate human immune response, the researchers say.

"In an immune-competent patient, the immune system will fight the virus, and most adults are immune against measles since they have been vaccinated against the disease in childhood or have had measles," said Christian Beltinger, M.D., an associate professor at the University Children's Hospital in Ulm. "Although cancer patients are immune-compromised by their disease or because of therapy, they still may mount a sufficient attack against vaccine measles virus."

To trick this immune surveillance, the researchers generated blood outgrowth endothelial cells (BOECs), which are produced outside of the body using human blood bathed in a cocktail of growth factors. "They do not naturally occur in the blood, but they are derived from endothelial progenitor cells, rare cells that are produced in the bone marrow and shed into the blood," Dr. Beltinger said.

These cells are well suited for cancer therapy for two reasons, he said. If a vaccine measles virus is tucked within them, it can't be reached by the immune system's neutralizing antibodies. Also, they are endothelial progenitor cells, which are recruited in the body wherever new blood vessels are formed.

"Tumors need vessels to grow, hence they recruit these blood progenitor cells," Dr. Beltinger said. "That makes them home to the tumors."

BOECs have been used for other gene therapeutic approaches, such as for hemophilia, but this is the first time they have been adapted to carry vaccine measles virus, he said.

To test how well they functioned as a cancer therapy, the researchers injected U87 cells (the most commonly used human glioma cancer cell line) into the brains of immune-compromised mice. Once the tumors were established, BOECs recently infected with vaccine measles virus were injected around, but not into, the brain tumor. These loaded blood cells navigated through normal brain tissue to the tumor mass, and once inside, the BOECs released the virus into surrounding tumor cells. It then spread to other tumor cells.

Eventually the blood cells died. This delay of death, however, was sufficient to allow the infected cells to home to the tumor and release the virus, the researchers say.

They found that mice treated with BOECs survived significantly longer than mice receiving just empty blood cells or "naked" measles virus. But the researchers say that all mice eventually died, showing that the therapy could not completely eradicate the tumors.

"While these modified blood cells carrying vaccine measles virus look like a promising novel therapy for gliomas, it is still a preclinical experimental approach," Dr. Beltinger said. "Potentially it could be used on most malignant gliomas, including glioblastomas, because the targeting of the virus can be genetically modified.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Cancer Tip: Of Asthma and Aspirin, Two Studies Highlight Role of Inflammation in Cancer

registration@aacr.org () — Mon, 16 Apr 2007 12:00:00 GMT

LOS ANGELES - Can reducing inflammation keep cancer at bay? Two novel studies presented at the 2007 Annual Meeting of the American Association for Cancer Research that examine use of common anti-inflammatory agents suggest this might be the case. One large study found that women who regularly use aspirin developed fewer cancers than women who did not, while another, conducted in mice and now being confirmed in an analysis of breast cancer patient records, discovered a link between asthma and an increased risk of cancer metastasis to the lungs.

Both studies offer hope that managing inflammation can help control cancer.

Association of aspirin and non-aspirin NSAIDs with cancer incidence and mortality in a large prospective cohort study: Abstract 3400

Regular aspirin use was associated with lower cancer incidence and cancer mortality, but non-aspirin non-steroidal anti-inflammatory drug (NSAID) use was not, according to one of the largest studies ever conducted to look at the impact of these agents on overall cancer risk. Aspirin was also associated with a lower risk of dying from coronary heart disease, while NSAIDs were not.

Among 22,507 cancer-free postmenopausal women who participated in the Iowa Women's Health Study and provided information on aspirin and NSAID use, those who said they regularly used aspirin had a 16 percent reduced risk of developing cancer more than a decade later, as well as a 13 percent reduced risk of dying from cancer over this same time period, compared to women who did not use aspirin. But there was no statistically significant impact on cancer incidence or mortality among women who used non-aspirin NSAIDs, compared to those who did not, say researchers from the Mayo Clinic, in Rochester, Minnesota.

The researchers also looked at whether smoking status had any impact on the potential preventive effects of aspirin and found that while these agents were associated with lower cancer incidence and mortality among former and never smokers, the same apparent benefits were not seen among active smokers.

These study results do not mean, however, that women should throw away their NSAIDs or pick up a bottle of aspirin, says the study's lead author, Aditya Bardia, M.D., M.P.H. "This is just one study," he says. "However, it does provide provocative evidence that regular aspirin use may play a role in preventing the most common chronic diseases in western countries, namely cancer and heart disease."

The different impact of aspirin compared to other NSAIDs was somewhat surprising, the researchers say. "While chemically different, these agents share at least one similar mechanism of action so you might have expected them to have comparable effects," says Jon Ebbert, M.D., the senior author on the study.

Specifically, aspirin and other NSAIDs reduce inflammation through inhibition of cyclooxygenase (COX) enzymes. These enzymes are responsible for the formation of prostaglandins, which can drive inflammation and possibly stimulate cancer development in a number of organ sites, Dr. Ebbert said.

Previous studies have evaluated whether aspirin or other NSAIDs prevent specific cancers, such as breast cancer. "But this study is unique because we were able to evaluate comprehensive endpoints such as total cancer incidence and cancer mortality, which are more clinically relevant outcomes for patients," Dr. Bardia said.

While the researchers note that one of the weaknesses of this study was that the women were given only a single survey of aspirin and non-aspirin NSAID use, it also had many strengths including the prospective cohort study design, relatively long follow-up (up to 12 years) on a large number of participants, during which time many developed (3,487) and died (1,193) from cancer. The authors were also able to adjust the results for a large number of lifestyle factors, and found little evidence that these other factors could explain the aspirin and cancer associations observed in this study.

Chronic allergen provocation results in a significant increase in the rates of lung metastasis that is dependent on induced pulmonary inflammation: Abstract 2553

An intriguing study, conducted in mice and supported by an ongoing examination of breast cancer patient records, suggests a link between the pulmonary inflammation seen in asthma and increased risk of lung metastasis.

The study, conducted by researchers at Mayo Clinic Arizona., suggests that breast cancer patients who have asthma could reduce their risk of cancer spread by using readily available inhaler medications.

"A link between pulmonary inflammation and lung metastasis would not only have significant effects on patient diagnosis and care, but will also immediately affect the way breast cancer patient are treated," said Anna Taranova, M.D., a senior research fellow in the laboratory of James Lee, Ph.D. at Mayo. "Those with asthma might be able to reduce their risk of lung metastasis, and increase their survival, with aggressive corticosteroid treatment."

Furthermore, the findings could prove to be relevant to asthma patients diagnosed with other cancers that metastasize to the lungs, according to Dr. Taranova.

"We suspect that the relationship between lung inflammation and metastasis will not be limited to breast cancer patients," Dr. Taranova said.

The researchers say these results, along with findings from their other recent research, offer a biological link: activation of cells that line blood vessels is required both for the movement of pro-inflammatory white blood cells into lung tissue (as occurs in asthma) and for the movement of circulating cancer cells from the blood into lung tissue.

In this study, mice were exposed to an aerosolized allergen commonly used in mouse asthma studies and then were injected with melanoma cells. Three other groups of mice were also studied: control mice; mice that received the human corticosteroid allergy and asthma therapeutic agent budesonide after exposure to the allergen; and mice treated with an antibody to eliminate CD4+ T cells before exposure to allergen. (CD4+ T cells orchestrate immune responses to allergens and are largely responsible for the lung inflammation that occurs in asthma.) Metastasis was continually assessed in all groups.

The researchers found that allergen-induced pulmonary inflammation was associated with an almost 400 percent increase in lung metastasis in the mice. But in mice treated with either an antibody to deplete CD4+ T-cells or budesonide to reduce their allergic lung inflammation, the rate of metastasis fell to that seen in mice that were not exposed to allergen. "The treatments wiped out the increases in the rate of metastasis induced by allergic inflammation, reducing the observed rates of metastasis to those found in mice that never experienced the allergen," Dr. Taranova said.

The researchers are now working with epidemiologists at Mayo Clinic Rochester to determine if breast cancer patients with lung metastasis had higher than normal rates of asthma. To date, they have found "productive and provocative results," Dr. Taranova says: over 20 percent of women with breast cancer who developed lung metastasis also appear to have had a previous diagnosis of asthma. The typical frequency of asthma occurrence in U.S. women is, at most, eight percent, she said.

"Our long term goal is to continue this detailed retrospective study of breast cancer patients, eventually translating these studies into a multi-center prospective examination of cancer patients," Dr. Taranova said. "We want to define the specific parameters that link lung metastasis and pulmonary disease."

The researchers say that many questions need to be answered, including whether asthmatics who regularly use anti-inflammatory corticosteroids experience a side benefit of reduced risk for lung metastasis, and whether people who have allergies, but not asthma, are at the same risk.

Dr. Taranova believes these findings are surprising, as the researchers originally suspected that patients with asthma would have limited lung metastasis. "However, as in most things in science, we have learned much more from studies disproving our flawed hypotheses than from studies confirming our preconceived ideas," she said.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Prognosis: Predicting Cancer Risk in the Long-Term

registration@aacr.org () — Mon, 16 Apr 2007 12:00:00 GMT

LOS ANGELES - Every day, people make assumptions, educated and not, about their risk for developing cancer. For many, the risk of developing a secondary cancer after an earlier illness rests uncomfortably in the backs of their minds. Researchers are continuing to understand the factors that might dictate an individual's risk of developing primary or secondary cancer. The risk of developing cancer depends on the subtle interplay of genetics, personal choice and the environment, according to several long-term studies presented today at the 2007 Annual Meeting of the American Association for Cancer Research.

Parity, Breastfeeding, and Breast Cancer Risk by Hormone Receptor Status in Women with Late Age at First Birth-A Case-Control Study: Abstract 2610

Research has shown there is a connection between reproductive factors-such as age at first birth, number of births, and breastfeeding-and a woman's risk of breast cancer. Yet to be established is how these factors interact, and whether they have differing effects on risk for breast cancers that are estrogen and progesterone receptor positive (ERPR-positive) versus those that are not (ERPR-negative).

A new study by a team of researchers in the U.S. and Australia suggests that breastfeeding may help protect women against both subtypes.

"Our previous research had shown differing effects of these reproductive factors on ERPR-positive and ERPR-negative breast cancers, and we wanted to understand them better," said study co-author Giske Ursin, M.D., Ph.D., associate professor in the Department of Preventive Medicine at the University of Southern California's Keck School of Medicine. "Our most important finding here is that breastfeeding seems to modify the increased risk that comes from having children later in life."

The study looked at 995 women with invasive breast cancer (729 ERPR-positive, 267 ERPR-negative), and 1498 controls, aged 55 years or older who participated in the Women's Contraceptive and Reproductive Experiences Study, a multicenter study of breast cancer in white and African-American women. The researchers considered women's age at first birth, the number of births - referred to as parity - and whether or not they had ever breastfed.

Women with a first birth before age 25 had 41 percent lower relative risk of developing ERPR-positive breast cancer than women with no births; this protective effect did not hold true for women who gave birth at or after 25. The latter group also had double the risk of developing ERPR-negative cancers. "What we find is that early age at first birth protects against ERPR-positive cancer, but not receptor-negative," Ursin said.

More notable, researchers said, was their finding related to age at first birth and parity. Breastfeeding was protective for both subtypes, regardless of when a woman gave birth.

"The protective effect of parity on ERPR-positive cancers was seen only among women who breastfed, but not among those who never breastfed," said Ursin. "And for women giving birth after age 25, parity was associated with increased risk for both types of breast cancer only in women who had never breastfed."

The researchers concluded that breastfeeding may lessen the increased risk that comes from having children later in life. According to Ursin, breastfeeding may act through different hormonal mechanisms than early age at first birth and parity.

For now, the study suggests that women who delay childbearing should consider breastfeeding when they do have children. "We suspect that women can reduce the increased risk that comes with later childbearing by choosing to breastfeed," Ursin said.

Second Cancers among 104,760 Survivors of Cervical Cancer: Evaluation of Long-Term Risk: Abstract 3396

Women diagnosed with cervical cancer tend to have good long-term survival, but they often have specific risk factors for developing a cancer later in life: a history of smoking, infection with the human papillomavirus, and/or treatment with radiation therapy.

A study by researchers in the U.S., Denmark, Finland, Sweden, and Norway has documented cervical cancer survivors' significantly increased risk of developing a second primary cancer-a risk that lasts for several decades after their initial diagnosis of invasive cervical cancer. Using 13 population-based cancer registries in Denmark, Finland, Sweden, Norway, as well as the U.S. Surveillance, Epidemiology, and End Results program, the researchers studied 104,760 cervical cancer survivors starting one year after their diagnosis and continuing over the next 40 years or more. They found that these women had a 30 percent higher incidence of all second cancers compared to women in the general population.

"The unique aspect of this study is the long length of follow up," said Anil Chaturvedi, Ph.D., MPH, a researcher at the Division of Cancer Epidemiology and Genetics, National Cancer Institute. "Previous studies had evaluated second cancer risk up to 30 years of follow up. With these registries, we were able to assess longer-term risk over 40 years or more."

The researchers examined the women's risk for specific cancers associated with smoking and HPV infection - known causes of cervical cancer. "We did not have information on smoking in our study, but it has been well-documented that women with cervical cancer are more likely to have a history of smoking," Chaturvedi said.

Compared to women in the general population, risks for HPV-related cancers (oropharynx, female genital sites, and anus) and smoking-related cancers (lung, pancreas, and urinary bladder) were significantly elevated.

The researchers also compared second cancer risk in women who had radiation treatment versus women in the general population. Women who underwent radiation were at increased risk for any second cancer and cancers at heavily irradiated sites (colon, rectum/anus, urinary bladder, ovary, female genital sites) beyond 40 years of follow up.

"What's most significant is that even as far out as 40 years after diagnosis, these women have an increased risk for second cancers," Chaturvedi said. "These results suggest a need for close medical surveillance for second cancers."

Genetic Instability and Development of Second Primary Tumors after Hodgkin's Disease: Abstract 1949

Thanks to treatment advances, the majority of people diagnosed with Hodgkin's disease - often in youth or early adulthood - can expect to survive long-term. However, about 10 percent of them will eventually develop another form of cancer in the decades after finishing treatment.

Researchers at The University of Texas M. D. Anderson Cancer Center have discovered that genetic instability may help predict which subset of patients is at greatest risk for second cancers-which, in turn, could pose important implications for their treatment and long-term follow-up.

"It is particularly devastating for young adults to be hit with Hodgkin's disease, do well, and then face another cancer ten to 20 years down the line," said Rand El-Zein, M.D., Ph.D., an assistant professor of epidemiology at M. D. Anderson. "Cytogenetic and chromosomal abnormalities have already been validated as such as markers of cancer risk. We wanted to find out if there are genetic markers that can serve as predictors of second primary tumors."

The study analyzed chromosomal aberrations in lymphocytes collected from 252 adult Hodgkin's disease patients before they began treatment between 1986 and 1992. Their analysis focused on the number of chromatid breaks during 100 complete cell metaphases. Researchers found a strong correlation between the number of breaks and the likelihood of developing a second cancer.

At a follow-up of approximately 13 years, 27 patients, or 11 percent, developed second primary cancers: five solid tumors, four leukemia, eleven skin cancers, and seven lymphomas. These patients had significantly higher levels of total breaks than patients who remained cancer-free. The 25 percent of patients with the highest number of breaks were almost two-and-a-half times more likely to develop second cancers.

"We believe that these chromosomal aberrations explain why some patients develop second primary cancers and some don't," said El-Zein. She also noted that this information could potentially be useful in tailoring treatment regimens and follow-up surveillance.

"For a patient with a higher level of genetic instability, you might want to give them a less toxic regimen, or spread out the treatments more, or give them some kind of agent to boost their genetic repair mechanisms," said El-Zein. "Or you might want to do closer surveillance in the years after treatment."

The research team is now looking at other potential predictors of second cancer risk, such as polymorphisms in the DNA repair genes, and plans to analyze samples taken from the same patients over time. Information about each patient's treatment regimen also will help them determine if there is a correlation between genetic instability and toxicity from the treatment.

"Being able to predict the likelihood of a second cancer has great potential to be helpful not only for Hodgkin's disease survivors, but for survivors of any cancer that is associated with later risk of a secondary cancer," El-Zein said.

Risk of Second Malignant Neoplasms after Childhood Leukemia and Lymphoma: An International Study: Abstract 3395

A team of 19 researchers from Australia, Canada, Iceland, Singapore, and several European countries has completed what they call the "largest population-based study of absolute and relative risk of second malignant neoplasms (SMNs)" in childhood leukemia and lymphoma survivors. The study, which analyzed data from 13 cancer registries in several countries, found that these survivors have a higher-than-average risk of developing a different type of cancer later in life.

"Large-scale, long-term population studies are necessary to have a better understanding of the risk of second primaries among cancer patients," said study coordinator Paolo Boffetta, M.D., MPH, of the International Agency for Research on Cancer. "Most of the second primary cancers after a childhood cancer are, fortunately, rare. One therefore needs large series of patients to precisely estimate risks."

The registries used had been active for at least 25 years and covered different time periods between 1943 and 2000. Each provided individual data on leukemia, Hodgkin's lymphoma, and Non-Hodgkin's lymphoma, along with second cancers - new primaries, not recurrences or metastases - in children from infancy through age 14. The researchers' analysis found that the cumulative incidence of second cancers was 2.43 percent, 12.7 percent, and 2.5 percent within 30 years since leukemia, Hodgkin's lymphoma and Non-Hodgkin's lymphoma, respectively.

According to the researchers, this means that survivors of these childhood cancers are considered to be "high risk" for developing second cancers. This is especially true for Hodgkin's lymphoma survivors: one in eight was affected within 30 years from the initial diagnosis.

"This is probably due to the better survival of Hodgkin's lymphoma patients who received highly toxic chemotherapy, as compared to other groups of patients," Boffetta said. "In other words, chemotherapy, possibly in combination with radiotherapy, increased the survival of Hodgkin's lymphoma patients but also their risk of developing a second cancer."

In Hodgkin's lymphoma survivors, researchers observed an increased risk for brain, thyroid, breast, and nonmelanoma skin cancer, as well as leukemia.

The study could not assess whether risk of a second cancer varied among children who were treated in the 1940s, 50s, or 60s versus more recent decades, due to the limited follow-up time for the latter population. According to Boffetta, their risk estimates are based on patients who had past treatment regimens - those for whom they have enough follow-up to make proper estimates. Those estimates may not reflect the risk entailed by more recent, and presumably less toxic, regimens.

"The significance of these results for adult survivors of childhood cancers is that they provide a more precise estimate of their risk of developing a second primary cancer," Boffetta said.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
267-646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
213-765-4202

Study Produces Conflicting Findings on the Use of Anti-Anemia Drug

registration@aacr.org () — Mon, 16 Apr 2007 12:00:00 GMT

LOS ANGELES - Results from a phase III drug trial indicate that an anti-anemia drug did not significantly decrease the need for blood transfusions in patients not on chemotherapy, and decreased overall patient survival when compared to placebo, according to researchers from the UCLA Medical Center at the 2007 Annual Meeting of the American Association for Cancer Research.

The drug, darbepoetin alfa (DA) is a synthetic form of erythropoietin, a hormone that signals the formation of new red blood cells from within the bone marrow. DA is commonly used as a means of combating anemia in cancer patients who are also receiving chemotherapy. Anemia in cancer patients can result from either chemotherapy or the cancer itself, and it has a measurable effect on quality of life and overall cancer survival.

While some cancer patients not undergoing chemotherapy are also given DA, previous placebo-controlled studies did not show that darbepoetin significantly reduced transfusion risk.

"While the study was not specifically designed to study survival rates, our results indicate a statistically significant decrease in patients given the drug versus those who were given placebo," said John Glaspy, M.D., professor at the University of California, Los Angeles School of Medicine. "Since erythropoietic agents are sometimes used in the U. S. to treat anemia and reduce transfusion risk in patients not on chemotherapy, these results are of concern to the research and clinical cancer communities."

The trial was designed to examine the ability of darbepoetin to reduce the need for blood transfusions in patients with active cancer not undergoing chemotherapy. The trial, held in clinical sites throughout North America, Europe and Australia was supported by the drug's manufacturer, Amgen.

Approximately 1,000 people were enrolled in the study, which was open to patients with most forms of cancer, except myeloid or acute leukemia and Burkitt's or lymphoblastic lymphoma. The most common cancers were non-small cell lung, breast and prostate cancer, with 82 percent of patients in disease stage III or IV.

Patients were randomly assigned to receive either DA or a placebo, and given a weekly dose until week 16 or until the patient required a blood transfusion. The patients were then given an end-of-study examination at week 19, with two years of follow up to evaluate survival. During the study, researchers monitored each patient's hemoglobin level, an indicator of red blood cell production. Darbepoetin was withheld if the patient's hemoglobin count exceeded 13 grams per deciliter.

According to the researchers, fewer patients in the darbepoetin group required transfusions during the study, but the overall difference between the darbepoetin and placebo groups was not statistically significant. Subsequent analysis also showed a statistically significant increase in patient deaths - during the trial and in the follow up - amid the darbepoetin arm of the trial versus the placebo group, with 136 darbepoetin patient deaths versus 94 in the placebo group. Researchers say the trial was not designed to focus on survival, prognostic factors were not balanced at baseline and no specific study procedures were undertaken to determine the exact cause of death for these patients, beyond investigator attribution.

One confounding aspect of these study results was the different reactions among patients in the darbepoetin group, says Glaspy. When treated with darbepoetin, patients with kidney, prostate, or stomach cancers, non-Hodgkin's lymphoma, or multiple myeloma appeared to have worse survival outcomes. However, the opposite was seen among patients with breast, colon, ovarian, or cervical cancer. Indeed, many of these patients also achieved higher hemoglobin counts (yet still within the study's safety parameters). Survival rates were also better for patients in either group who did not need to receive transfusions.

"People with cancers like myeloma and lymphoma did substantially worse than people with diseases like breast cancer, for example," Glaspy said.

When the researchers notified Amgen of their preliminary results, the company issued a warning to doctors and informed the Food and Drug Administration as to the results of the trial. Subsequently, the manufacturer and FDA agreed to a "black box" warning for doctors about the drug's safety in this particular circumstance. "Certainly, the first concern is about safety, although nobody wants to see an increase in transfusions among patients already on the medication and doing well," said Glaspy.

"The findings will pose a particular puzzle to cancer researchers, as the exact mechanisms behind the observed decrease in patient survival is not clear," Glaspy said. "Likewise, we'll need to resolve these data in light of evidence that darbepoetin offers benefits for patients with certain types of cancer when used within chemotherapy. There are no obvious reasons for this discrepancy.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Cetuximab and Irinotecan Combination Increases Survival in Metastatic Colorectal Cancer, EPIC Trial Researchers Report

registration@aacr.org () — Mon, 16 Apr 2007 12:00:00 GMT

LOS ANGELES - A phase III trial of 1,298 colorectal cancer patients has found that a combination of the drugs cetuximab (Erbitux) and irinotecan showed a significant improvement in progression-free survival over just irinotecan alone, according to an international team of researchers.

The Erbitux Plus Irinotecan in Colorectal Cancer (EPIC) study looked at survival in metastatic colorectal cancer patients who had already shown resistance to conventional therapies. The research was presented today at the 2007 Annual Meeting of the American Association for Cancer Research.

By the end of the study, a significantly larger number of patients who received the combination of cetuximab, an antibody against the epidermal growth factor and irinotecan, an enzyme-inhibiting cancer drug, survived without their cancers progressing further. The tumor response rate in this group was also significantly higher. The study was sponsored, in part, by Bristol-Myers Squibb and Merck KGaA.

"Patients who received both cetuximab and irinotecan experienced longer periods of time spent, on average, without further progression of the disease," said Alberto F. Sobrero, M.D., of the San Martino Hospital's Department of Medical Oncology in Genoa, Italy. "From a patient perspective, any improvement in progression-free survival, as well as tumor shrinkage, is worthwhile. These data confirm that, despite a moderate increase in side effects, cetuximab is a key therapeutic agent in the optimal treatment of advanced colorectal cancer."

The EPIC trial was designed to study the overall survival in patients treated with both cetuximab and irinotecan, with secondary objectives that include response rate and progression-free survival. Patients eligible in the trial had to have shown resistance to the drug oxaliplatin, a platinum-based therapy commonly used in the treatment of colorectal cancer.

The trial participants, enrolled from cancer centers across Europe, Australia and the United States, were primarily male (62.9%) and Caucasian (91.6 %), with a median age of 62. The patients were randomly placed in groups to receive irinotecan every three weeks or irinotecan plus cetuximab every three weeks, and were treated until their disease progressed.

Once the cancer progressed, the researchers stopped study treatment, and further treatment was at the discretion of the patient's physician. According to Sobrero, 16 percent of patients who received both medications responded to the treatment versus four percent of patients who received irinotecan alone.

Despite these positive findings, there was no difference in overall survival between the two arms in this study. Nearly half of the patients, who were initially treated with irinotecan only, were given cetuximab when their cancers progressed. Therefore, many patients in both arms actually received the same treatment, which the researchers say could explain the lack of difference in overall survival between the two arms.

The EPIC researchers reported a comparative increase in side effects for the patients who received the combination therapy, including fatigue, diarrhea and an acne-like rash previously associated with cetuximab.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Cetuximab Increases Survival in Advanced Colorectal Cancer Patients, Studies Show

registration@aacr.org () — Mon, 16 Apr 2007 12:00:00 GMT

PHILADELPHIA -- Research presented today at the 2007 Annual Meeting of the American Association for Cancer Research confirmed that there is now an effective treatment option for colorectal cancer patients for whom all other treatment options have been exhausted - cetuximab.

In a study of 572 colorectal cancer patients, researchers in Canada, Australia, New Zealand and Singapore found that cetuximab, marketed under the brand-name Erbitux®, improved survival time and slowed progression of the disease. Support for the study was provided by Bristol-Myers Squibb Company and ImClone Systems Incorporated.

"Cetuximab improved survival in these patients when all other therapies had failed," said Derek Jonker, M.D., assistant professor at the University of Ottawa and Canadian co-chair of the study. "This is the first time a single agent biologically targeted therapy has demonstrated a survival advantage in patients with colorectal cancer, and it is also the first time an EGFR-targeting drug has achieved this goal."

Conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG), the study, called CO.17, was a randomized, multi-center, phase III trial. It compared cetuximab plus best supportive care to best supportive care alone in patients with metastatic colorectal cancer whose disease was no longer responding to all available chemotherapy, including irinotecan, oxaliplatin and fluoropyrimidines.

The goal of the CO.17 study was to evaluate the effect of cetuximab on survival in patients with advanced colorectal cancer who are without other options for treatment other than supportive care.

Study participants were randomly selected either to receive best supportive care alone, or best supportive care plus cetuximab intravenously weekly until the cancer progressed further. According to Jonker, the researchers defined best supportive care as any and all care given to alleviate symptoms of the cancer and to improve quality of life. The participants who were to receive cetuximab were given 400 mg of the drug intravenously at the outset of the trial, followed by weekly doses of 250 mg.

Cetuximab, an antibody against the epidermal growth factor receptor (EGFR), functions by binding to the receptor on the surface of cancer cells. This binding action prevents the activation of enzymatic pathways that lead to cell growth and proliferation. Cetuximab also enlists the body's immune system triggering "natural killer cells" to attack the cancer, a process called antibody dependent cell cytotoxicity.

Jonker and his colleagues followed the patients, assessing the status of the tumors every eight weeks by CT scan until the cancer began to progress. According to Jonker, the results of the CO.17 trial showed a statistically significant 23 percent improvement in overall survival (the primary outcome being studied) as well as a 32 percent reduction in the risk of disease progression (the secondary outcome being studied). The survival time of the participants was, on average, six months for the patients given cetuximab versus four-and-a-half months for patients who received best supportive care alone.

"Earlier studies demonstrated cetuximab could shrink colon tumors, both alone and when combined with chemotherapy," Jonker said. "While some patients receiving cetuximab in the CO.17 study had significant tumor shrinkage, many more had the cancer growth arrested, delaying progress of the disease and resulting in patients living longer."

"These promising results," Jonker said, "will lead to further National Cancer Institute of Canada trials in which cetuximab will be combined with other therapeutics to treat metastatic colorectal cancer."

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Diagnosis: New Diagnostic Technologies Offer Non-Invasive Means

registration@aacr.org () — Sun, 15 Apr 2007 12:00:00 GMT

LOS ANGELES - Molecular messages and signals circulating in blood or contained in cells lining the airway can identify early stage cancer, according to research reported today at the 2007 Annual Meeting of the American Association for Cancer Research. Scientists looking to apply basic science knowledge to medical practice are developing tests that diagnose, predict or monitor cancer risks, without invasive tissue sampling. Such tests could benefit all, particularly underserved populations, such as the poor, who often wait until symptoms appear before seeing a doctor.

Lung carcinogenesis tracked by DNA methylation mapping from exhaled breath of ambulatory subjects: Abstract 827

A series of quietly exhaled breaths might indicate whether or not a patient is at risk for lung cancer, according to researchers from the New York State Department of Health. Using DNA recovered from exhaled breath, researchers can examine the state of cells that line the lungs, and potentially detect cancer at an early stage, when treatment may be most successful.

"Early detection of lung cancer is vital, yet there is no current non-invasive means of identifying cancer in a clinical setting," said Simon Spivack, M.D., M.P.H, research physician in the Human Toxicology & Molecular Epidemiology Laboratory at the New York State Department of Health's Wadsworth Center. "We have found that exhaled breath contains DNA, we believe from the cells lining the lungs, which may then tell us whether that person is at risk for cancer."

Condensed exhaled breath has been used previously to detect small volatile molecules that could indicate both non-malignant and malignant, lung diseases. Dr. Spivack and his colleagues have shown, in a pilot study, that the large molecule DNA could also be recovered albeit in trace amounts in exhaled breath condensate.

In particular, the researchers looked to see if the DNA they captured had been methylated, that is, tagged by a molecular "methyl" fragment, which blocks activation of the genes. The researchers analyzed the detailed methylation patterns of six tumor suppressor gene promotors, regions of DNA that serve as regulators of gene transcription. When those promoter regions become methylated, the cell can no longer activate its tumor suppressor genes.

It is not necessary to methylate every promoter region to induce cancer, the researchers say, so they study detailed variations in the patterns of methylation among selected gene promoters in different patients. Dr. Spivack and his colleagues believe that categorizing patients according to these methylation patterns can potentially evaluate a patient's predisposition to lung cancer. The pilot study of 33 individuals showed statistically apparent differences between never-smokers, former and current smokers, and those with lung cancer.

According to Dr. Spivack, their findings could represent a considerable advance in the early detection of lung cancer. He posits a scenario in which breath or other non-invasive tests such as CT scans can serve as cost-effective pre-screening tools for lung cancer, and could allow for treatment at early stage when the patient would theoretically have the best chance of success.

CD44 Expression in Oral Rinses: A Potential Early Detection Strategy for Head and Neck Cancer: Abstract 3506

A simple oral rinse could detect the early development of head and neck squamous cell carcinoma, according to researchers at the University of Miami's Sylvester Comprehensive Cancer Center. Their strategy involves the detection of CD44, a protein biomarker for HNSCC tumors, combined with the detection of cancer-related altered DNA, and could reliably distinguish cancer from benign diseases.

Currently, only 50 percent of head and neck cancer patients are cured of the disease. While late-stage HNSCC has a poor prognosis, cure rates exceed 80 percent if caught early enough.

"Head and neck cancers are devastating for all patients. They are particularly challenging for the poor and disadvantaged, who often do not have the adequate, regular care that makes early detection more likely," said Elizabeth Franzmann, M.D., assistant professor of otolaryngology at Miami. "Our study has shown that an oral rinse test, simple enough to be administered at any community health center, is likely to detect cancer about 90 percent of the time."

While CD44 appears on the surface of cells in healthy tissue, it is elevated at least seven- fold times in head and neck cancer. Dr. Franzmann and her colleagues theorized that CD44 could be detected in an oral rinse, which would flush out the CD44 protein by washing over the cellular membranes of interest in the throat and mouth.

According to Dr. Franzmann, their study began with an attempt to find if soluble CD44, alone, was sufficient to distinguish between cancer and other diseases. They collected oral rinses from 102 head and neck cancer patients and 69 control patients with benign diseases and history of tobacco or alcohol use. The test detected two patients with cancer or precancer before the disease was clinically evident. Furthermore, the study detected few false positives among the control group. However, they were only able to detect elevated levels of CD44 in 62 percent of cancer patients.

So, Dr. Franzmann and her colleagues looked for another potential marker of cancer: the hypermethylation of promoter genes. In many cancer cells, DNA can be chemically modified without changing the actual DNA sequence. This hypermethylation process can encourage the growth of cancer by effectively shutting down the genes that control the cell's growth cycle.

According to Dr. Franzmann, an oral rinse sample contains enough cells to determine the presence of hypermethylated DNA. A pilot study showed that hypermethylation could be found in oral rinse samples from nine out of 11 head and neck cancer patients who had low levels of soluble CD44 from the original study.

"If put into practice, an oral rinse screening test for head and neck squamous cell cancer could be more effective than the PSA test for prostate cancer," Dr. Franzmann said. "Many lives could be saved through a test that is no more invasive than gargling."

Smart Hydrogel Nanoparticles for Serum Cancer Biomarkers Harvesting: Abstract 2470

Researchers at George Mason University are investigating a remarkable use of nanotechnology that might change the way doctors monitor patients for cancer-indicating biomarkers. These hydrogel nanoparticles, less than one tenth the size of a red blood cell, could function like "smart" sponges, designed to soak up specific proteins in the bloodstream.

According to the researchers, it is conceivable in the future to inject these nanoparticles in the bloodstream, allow them to run through the circulatory system and then harvest them by simple blood withdrawal for analysis. While the nanoparticles are considered to be biologically inert, proper safety trials will have to be performed before their use in patients. In the meantime the particles can be used to harvest candidate biomarkers from a tube of blood drawn from patients.

"There is a tremendous need to identify cancer biomarkers but the biggest problem is that they are usually present in only very minute amounts in the blood," Alessandra Luchini, Ph.D., a post-doctoral researcher at George Mason University' Center for Applied Proteomics and Molecular Medicine. "We can engineer hydrogel nanoparticles to look for a single biomarker, or a multitude of selected molecules, amid a relatively vast volume of blood."

The hydrogel nanoparticles are built as a lattice of plastic individual components, arranged at the nanoscale, about a millionth of a meter long. The nature of the individual components allows the researchers to modify the size of the holes in the lattice to form sponge-like pores small enough to catch a single protein biomarker.

To entice biomarkers into the pores, Luchini and her colleagues are using "bait" that is specific for either a class of molecules or an individual biomarker. The bait could consist of an electrical charge that can pull the biomarker into an engineered pore or it could consist of sticky molecule, like an antibody, that is designed to adhere to the biomarker's unique shape.

Once it has captured a biomarker and been removed from the patient through a simple blood withdrawal, the hydrogel can be electrically treated to coax biomarkers out of the particles.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Diet and Lifestyle: In the Cancer Fight, Eating Well is the Best Revenge

registration@aacr.org () — Sun, 15 Apr 2007 12:00:00 GMT

LOS ANGELES - We all know that eating fruits, vegetables and soy products provides essential nutrition for a healthy lifestyle, while obesity leads to the opposite. Yet proving the effect of nutrition, or obesity, on cancer is an experimental challenge and a focus for scientists. According to emerging evidence being presented at the 2007 Annual Meeting of the American Association for Cancer Research, eating well might still be one of the more pleasurable ways to prevent cancer and promote good health.

A novel mechanism for the chemoprotection by 3,3-diindolylmethane (DIM) and genistein for breast and ovarian cancer: Abstract 4217

Eating such foods as broccoli and soy are believed to offer some protection against cancer, but how this occurs is not well-understood. Now, in laboratory experiments, researchers at the University of California, Los Angeles, have discovered a biological mechanism whereby two compounds in these foods might lower the invasive and metastatic potential of breast and ovarian cancer cells.

They found that diindolylmethane (DIM), a compound resulting from digestion of cruciferous vegetables, and genistein, a major isoflavone in soy, reduce production of two proteins whose chemotactic attraction to each other is necessary for the spread of breast and ovarian cancers.

When applying purified versions of DIM and genistein to motile cancer cells, the researchers could literally watch these cells come to a near halt. When either compound was applied, migration and invasion were substantially reduced.

"We think these compounds might slow or prevent the metastasis of breast and ovarian cancer, which would greatly increase the effectiveness of current treatments," said Erin Hsu, a graduate student in molecular toxicology. "But we need to test that notion in animals before we can be more definitive."

Both DIM and genistein are already being developed for use as a preventive and a chemotherapy treatment for breast cancer, although more extensive toxicological studies are necessary, the researchers say.

The researchers looked at the potential of DIM and genistein to interfere with the "CXCR4/CXCL12 axis," which is known to play a central role in the metastasis of breast cancer and is also thought to play a role in the development of ovarian cancer. Primary cancer cells express very high levels of the CXCR4 chemokine receptor on the surface of their cells, and the organs to which these cancers metastasize secrete high levels of the CXCL12 chemokine ligand. This attraction stimulates the invasive properties of cancer cells and acts like a homing device, drawing the cancer cells to the organs they metastasize to.

When breast and ovarian cancer cell lines are exposed to purified DIM or genistein, levels of CXCR4 and CXCL12 messenger RNAs and proteins decrease in a dose-dependent manner, compared to untreated cells, according to Hsu.

To assess whether the compounds had any effect on the metastatic potential of the cells, the researchers placed the cells in one end of a compartment and watched how they moved toward CXCL12 at the other end. "The cells degrade the extracellular matrix in the upper compartment in order to move toward CXCL12 in the lower compartment, a system that represents a cell culture model for invasiveness," she said.

But if the cells are treated with either DIM or genistein, movement toward CXCL12 is reduced by at least 80 percent compared to untreated cells, the researchers say.

Hsu says that this same chemotactic attraction is thought to play a role in the development of more than 23 different types of cancer, and, so far, they have found that messenger RNA expression of CXCR4 and CXCL12 is substantially reduced when melanoma and prostate cancer cells are treated with the two compounds.

"We have also tested other phytochemicals and seen similar effects, indicating that this mechanism may mediate protective effects of other vegetable products as well," Hsu said.

The amount of DIM and genistein used in this study is probably comparable to use of a high dose of supplements, and is likely not achievable through consumption of food alone, the researchers say.

Flavonols and pancreatic cancer risk: The Multiethnic Cohort Study: Abstract 856

A study of food consumption in 183,518 residents of California and Hawaii has found that a diet high in flavonols might help reduce pancreatic cancer risk, especially in smokers. These compounds are generally ubiquitous in plant-based foods, but are found in highest concentrations in onions, apples, berries, kale and broccoli.

People who ate the largest amounts of flavonols had a 23 percent reduced risk of developing pancreatic cancer compared to those who ate the least, according to a research team led by Laurence Kolonel, M.D., Ph.D., at the Cancer Research Center of Hawaii.

Smokers gained the most benefit. Those who ate the most flavonols reduced their risk of developing pancreatic cancer by 59 percent, compared to those who ate the least, says the study's lead author, Ute Nöthlings, DrPH, who conducted the study as a postdoctoral fellow in Hawaii and is now a researcher at the German Institute of Human Nutrition Potsdam-Rehbruecke.

"The effect was largest in smokers, presumably because they are at increased pancreatic cancer risk already," said Nöthlings. Smoking is the only established risk factor for pancreatic cancer, and "short of stopping tobacco use, it has been difficult to consistently show lifestyle factors that might help protect against this deadly cancer," she says.

As part of a larger research project known as The Multiethnic Cohort Study, Kolonel and Nöthlings followed the participants for an average of eight years after they filled out a comprehensive food questionnaire.

Although Nöthlings says the study has a large statistical power because of the large number of pancreatic cancer cases (529) that occurred in the study population, she says that this one study cannot firmly answer the question of whether flavonols can prevent development of pancreatic cancer. "Further epidemiological studies in other populations and geographic regions are needed to confirm our findings," she said.

The study also is the first to examine prospectively specific classes of flavonols and pancreatic cancer risk.

The researchers looked at consumption of three flavonols: quercetin, which is most abundant in onions and apples; kaempferol, found in spinach and some cabbages; and myricetin, found mostly in red onions and berries.

Of the three individual flavonols, kaempferol was associated with the largest risk reduction (22 percent) across all participants. When the researchers divided intake into quartiles, and then compared highest intake to lowest, all the three classes of flavonols were associated with a significant trend toward reduced pancreatic cancer risk in current smokers, but not in never or former smokers. The interaction with smoking status was statistically significant for total flavonols, quercetin and kaempferol.

The researchers say their study did not examine the biological mechanisms by which these flavonols could exert a protective effect against pancreatic cancer. "But anti-carcinogenic effects of flavonoids in general have been attributed to the ability of these constituents to inhibit cell cycle, cell proliferation and oxidative stress, and to induce detoxification enzymes and apoptosis," Nöthlings said.

Polyp characteristics, diet, lifestyle factors and high-risk colorectal adenoma recurrence in the polyp prevention trial: Abstract 861

Experts agree that people who have had three or more potentially precancerous adenomatous polyps removed during a colonoscopy should be "rescoped" in three years to make sure the polyps do not recur. But now researchers at the National Cancer Institute (NCI) have identified other factors that independently raise the risk of recurrence.

Two of these risk factors - being over 65 years old, and male - cannot be modified, but the third - obesity - can, say the researchers.

The results can further help physicians stratify patients at greatest need for follow-up colonoscopies, they say, and can also inform patients about their own risk.

"In a situation where there are not enough physicians, or where doctors have long waiting lists for those who are not first-timers to a colon cancer check-up, then this risk stratification may help physicians prioritize which patients should be seen first," said Adeyinka Laiyemo, M.D., a cancer prevention fellow at NCI.

For patients, Dr. Laiyemo says that "it is important to follow your doctor's recommendation based on the nature of polyp removed during colonoscopy, and maintain a healthy weight. However, men should also recognize that they may be at a higher risk for developing worrisome polyps, and so should women who are over 65 years of age."

The researchers say the findings support the 2006 consensus guidelines, developed jointly by the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. These guidelines recommend that people with an advanced adenoma or three or more adenomatous polyps should undergo repeat colonoscopy in three years. The issue, according to the group, is that many patients were being rescoped earlier than recommended, and that these repeat colonoscopies constituted a significant portion of endoscopic practices, draining resources away from patients in need of first time screenings. Previous studies have found that a three-year interval was just as safe for people with three or more adenomatous polyps, high-grade dysplasia, or an adenoma one centimeter or larger in diameter.

This study was designed to see if these guidelines adequately identified patients who later developed dangerous polyps, and also sought to discover other factors associated with increased risk. The research team used data from participants in the Polyp Prevention Trial (PPT), which assessed the impact of a low-fat, high-fiber, high fruits and vegetables diet on polyp recurrence. They examined the diet, lifestyle, and polyp characteristics in 1,905 participants at baseline, after they had a colonoscopy in which at least one polyp was removed and before they altered their eating habits to conform to PPT rules.

Within four years, 230 PPT participants developed high-risk polyps, and 524 had a low-risk adenoma recurrence. Dr. Laiyemo and his team found that, indeed, the presence of multiple adenomas was the largest risk factor associated with polyp recurrence, but that age, gender and obesity played important, if lesser, roles in stratifying risk. Of these factors, age was the most statistically significant, followed by gender and then obesity, he reports.

The only statistically significant factor they found that lowered risk was use of non-steroidal anti-inflammatory drugs (NSAIDs).

"We know from previous studies that NSAIDs can reduce polyp formation, but perhaps at a cost, due to some side effects that have been observed," Dr. Laiyemo said. "We think that people should follow the consensus guidelines, but these other variables should also be considered when judging an individual's risk and the need for follow-up colonoscopies at the appropriate time."

Fruit and vegetable intake and head and neck cancer in a large United States prospective cohort study: Abstract 849

A new study among AARP members shows that just one additional serving of fruit and vegetables per day may lower your risk of head and neck cancer, but the data suggest that you may not want to stop at just one, according to researchers from the National Cancer Institute.

A large prospective study of 500,000 men and women aged 50 and older has found that those who ate more fruit and vegetables had a reduced risk of head and neck cancer. Head and neck cancer is the sixth leading cause of cancer-related mortality worldwide, resulting in more than 350,000 deaths annually.

"Identifying protective factors for head and neck cancer is particularly important as it has a high mortality rate," said Neal Freedman, Ph.D., cancer prevention fellow at the National Cancer Institute.

At the beginning of the study, participants reported their typical dietary habits on a food frequency questionnaire. Freedman and his colleagues followed participants for five years and recorded all diagnoses of head and neck cancer cases during this time.

In their findings, the researchers report that participants who ate six servings of fruit and vegetables per day per 1000 calories had 29 percent less risk for head and neck cancer than did participants who consumed one and a half servings per 1000 calories per day. Typically, adults consume approximately 2000 calories per day. One serving equals approximately one medium sized fresh fruit, one half cup of cut fruit, six ounces fruit juice, one cup leafy vegetables, or one half cup of other vegetables.

"Increasing consumption by just one serving of fruit or vegetables per 1000 calories per day was associated with a six percent reduction in head and neck cancer risk," Freedman said.

According to Freedman, people who ate a lot of fruit also tended to eat a lot of vegetables, and vice versa. To measure these two types of foods independently, the researchers included both fruit and vegetable intake in the statistical models, a common statistical approach. This allowed them to compare participants with different levels of fruit consumption while holding constant the level of vegetable intake and vice versa. When examining fruit and vegetable intake simultaneously, the protective association with vegetables seemed to be stronger than the association with fruits.

"Although we cannot absolutely rule out a cancer preventive role for other lifestyle factors that go along with eating more fruits and vegetables, our results are consistent with those from previous studies," Freedman said. "Our study suggests that fruit and vegetable consumption may protect against head and neck cancer and adds support to current dietary recommendations to increase fruit and vegetable consumption."

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Health Disparities: Genetics, Society and Race Play an Important Role in Access to Healthcare

registration@aacr.org () — Sun, 15 Apr 2007 12:00:00 GMT

LOS ANGELES - Minority individuals are much more likely to develop and die from cancer than the general U.S. population. Previous research points to lack of health insurance, poverty, language and cultural barriers, and inadequate access to early detection services and good medical care as causes. Research reported today at the 2007 Annual Meeting of the American Association for Cancer Research (AACR) suggests that genetics, in addition to socioeconomic status, are important factors accounting for the disparity of cancer incidence and mortality between African-Americans, Hispanics and Caucasians.

Exploring New Measures of Socio-Demographic Factors Associated with Later Stage of Cancer Diagnosis: Abstract 795

A survey of stomach and kidney cancer patients in Los Angeles revealed that those who were diagnosed in a late stage of disease - when cancer is harder to treat successfully - were likely to be older, living in an unsafe neighborhood and traveling at least 45 minutes to get to the doctor.

Researchers at the University of Southern California's Keck School of Medicine cite two general types of personal risk factors associated with late cancer diagnosis: socio-economic, or cultural, factors related to knowledge about the health care system and difficulties accessing it; and individuals' failure to give priority to medical care, despite having access to it.

While minorities have been shown to have higher rates of dying from cancer, it hasn't always been clear why, said Ann Hamilton, Ph.D., assistant professor of preventive medicine at USC. Using proportions of minorities in census tracts or income and education statistics hasn't been totally effective in identifying subgroups at higher risk.

Hamilton and USC colleague Myles Cockburn mailed a questionnaire to patients diagnosed with stomach and kidney cancer between 2000 and 2001 in Los Angeles County, which has a large Hispanic population. It asked about, among other things, access to care, acculturation, neighborhood environment, other diseases and demographic information. The acculturation scale was based on a series of questions, such as, ‘What language do you speak primarily at home - English, Spanish or both?'

Hamilton and Cockburn also wanted to identify "neighborhood-related" factors that could help predict population subgroups at higher risk for being diagnosed late, in addition to personal risk factors. "I wanted to identify new combinations of individual risk factors as well as ecological factors at the census tract level that could be used to better predict subgroups at higher risk," Hamilton said.

The researchers found that, at the census tract level, the percentage of people who speak a language other than English at home, the percentage of Hispanics 25 or older with less than a ninth grade education, percent unemployed and percent using public transportation were correlated with a higher percentage of cancers being diagnosed at a later stage.

"In using both ecological and personal measures, we were trying to determine how both factors may increase risk. We were assessing the effect of personal risk factors in the context of the neighborhood environment," Hamilton said. "For example, we found an indication that after taking other factors into account, a person with a lower level of acculturation who lived in an area where few others speak English was more likely to be diagnosed at a later stage of disease than the same type of person who lived in an area where most spoke English."

The results, Hamilton said, may help better target disease intervention programs for those most vulnerable and at risk.

The Effect of Hospital and Physician Volume on Racial Differences in Disease Recurrence Following Surgery for Prostate Cancer: Abstract 3416

Epidemiologists have unexpectedly found that African Americans had a higher rate of recurrence following prostate cancer surgery than did whites, regardless of whether or not patients received surgery at hospitals or by surgeons who performed a high number of such operations.

The findings were surprising as previous research has shown that, in general, patients fare better at hospitals that perform a high volume of surgeries or by surgeons who perform a large number of operations.

According to epidemiologist Kyna Gooden, Ph.D., of Shaw University, previous studies have shown that African Americans have a higher rate of prostate cancer recurrence and a greater likelihood of dying from their cancer following prostate surgery - more specifically, total removal of the prostate gland - compared to white men.

She and her co-investigators at Shaw University and the University of North Carolina in Chapel Hill, looked at whether the number of prostate cancer surgeries a hospital or a surgeon performed affected this disparity.

Gooden and her team hypothesized that a disproportionate number of African Americans were treated at hospitals or by physicians performing fewer surgeries. The racial differences in the prostate cancer recurrence and mortality following surgery would disappear, they assumed, once they took into account hospital and physician volume.

They examined data from the Surveillance, Epidemiology, and End-Results Medicare database for 962 African American and 7,387 white men diagnosed with prostate cancer between 1993 and 1999 who had received surgery within six months of diagnosis. They controlled for age at diagnosis, cancer stage and grade.

When the researchers looked at the outcomes after surgery in relation to volume, results were similar to previous findings - patients who had surgery at high volume hospitals for prostate cancer were less likely to have cancers that returned and less likely to die from prostate cancer. But when they broke down the numbers by race for African Americans and whites, they found that surprisingly, the racial disparities persisted.

"Even for patients who went to high volume hospitals and were seen by high volume physicians, there was still a racial disparity," Gooden said. "We expected that if everyone was treated by similarly experienced doctors or hospitals, they would have had comparable outcomes. But that wasn't the case."

"These results may have less to do with access to clinical care but more to do with lifestyle factors and the physical and genetic characteristics of the tumor itself," Gooden said.

Differential Gene Expression in Normal Breast Tissue from African American and Caucasian Women: Abstract 43

In preliminary findings, researchers have identified differences in the expression of two genes in normal breast tissue from African American and white women that could predispose the former to develop more aggressive tumors and poorer prognoses.

Postdoctoral fellow Lori Field, Ph.D., of the Windber Research Institute, and colleagues at Walter Reed Army Medical Center and Invitrogen Informatics, wanted to understand why breast cancer mortality rates are higher in African American women than in Caucasian, even though the overall incidence in white women is higher. Breast tumors in black women are larger, more aggressive, and more likely to spread to the lymph node than those in white women.

Before comparing breast cancer tumors, the scientists first examined healthy breast tissue. They obtained samples from 26 African American and 22 Caucasian women enrolled in the Clinical Breast Care Project, a federally mandated breast research program with both military and civilian centers.

Using microarray technology to examine large numbers of genes at once, they found differences in the expression of 89 genes among the two groups. Two of these genes - PSPH, phosphoserine phosphatase, which is involved in forming serine, and ACSM1, acyl-CoA synthetase medium chain family member 1, which is involved in fatty acid oxidation - had a higher expression in the African American women.

Serine is an intermediate in the synthesis of other amino acids, as well as DNA and lipids. If more serine is being shunted into any of these pathways, Field said, it might enhance cellular division and growth. Increased ACSM1 expression could increase the rate of fatty acid oxidation in the cell, resulting in a rise in cellular energy production.

"Both conditions could promote cell growth and could potentially provide greater growth advantage to breast cells in African Americans compared to Caucasians and could increase the likelihood to potential cancer transformation," Field said.

While the researchers continue to validate these initial findings, they currently are comparing breast tumors from African American and Caucasian women to look for differences in gene expression.

"If we see that there are differences in the breast tumors, we may find new molecular targets to which therapy can be tailored specifically to African American women," Field said.

Familial Breast Cancer in a Cohort of 59,000 African American Women: the Black Women's Health Study: Abstract 2500

Having a mother or sister with breast cancer significantly increases the risk for young African American women to develop breast cancer, according to the analysis of questionnaires answered by approximately 59,000 African American women enrolled in the Black Women's Health Study.

Beginning in 1995, questionnaires were given every two years to women - none of whom knowingly had cancer - asking about demographics, reproductive and health history, family history of breast cancer and other factors.

According to principal investigator Julie Palmer, ScD, professor of epidemiology at Boston University, few studies have examined the relationship of family history to breast cancer risk in African American women, and none have done so prospectively.

"We wanted to see if we would confirm what had been shown in white women - that having a mother or sister with breast cancer would increase a woman's risk of developing breast cancer," Palmer said.

Analyzing 10 years' worth of follow-up questionnaires found there were 1,050 cases of breast cancer among those who completed questionnaires on family history. The team, found that the incidence rate-ratio for such women was 1.77, meaning that overall, African American women who had a first degree relative - either a mother or a sister - with breast cancer had 1.77 times the risk of getting breast cancer compared to another woman of the same age who didn't have a family member with breast cancer. Having a family history of breast cancer was a stronger risk factor in women under 35, among whom the relative risk was 2.67.

Palmer said that as the study group ages and the number of women with cancer increases, the team can begin to examine other factors in cancer risk and development. "We'd expect that relative risk of 1.77 to go up quite a bit for women who have two first-degree relatives," she said. In fact, the researchers found that the overall relative risk for breast cancer was 2.58 for having two or more first-degree relatives with breast cancer, but the figure was based on few women.

The researchers plan to examine whether having a family member with other cancers is related to heightened breast cancer risk. Palmer noted that ovarian cancer might be one such cancer because "there are some shared genes," referring to the tumor suppressor gene BRCA1, which when damaged can increase a woman's risk of both breast and ovarian cancers.

In time, Palmer said, the study will have data to report on other cancers, such as colon and lung.

Compromised Complement System Increases Colon Cancer Susceptibility in African Americans: Abstract 2507

Genetic variations in the body's immune system could play a role in making African Americans more susceptible to developing colon cancer, scientists have found.

Researchers led by Krista Zanetti, Ph.D., a postdoctoral fellow in the National Cancer Institute's Division of Cancer Prevention and Center for Cancer Research, looked at variations in genetic sequences of the gene that makes mannose-binding lectin (MBL), a protein that plays a role in inflammation and innate immunity. They compared 26 MBL variations, or single nucleotide polymorphisms (SNPs), in 261 colon cancer patients and 537 normal controls in the Baltimore area.

Of the 26, four SNPs were associated with a significant increase in colon cancer risk in African Americans, though not in Caucasians. African Americans who carried two copies of all four variants had an approximately six-fold higher risk of colon cancer compared to those without such variants.

The four DNA variants occur in linkage disequilibrium - that is, they appear together at a higher frequency than by random chance - in both African Americans and Caucasians, though they are more prevalent in the former. "It was surprising," Zanetti said, "because we wouldn't necessarily assume that any one SNP would be linked to one race more than others. It wasn't our hypothesis."

Zanetti and her team currently are attempting to validate the findings with data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial, a randomized control trial originally designed to test the effectiveness of cancer screening methods. They will screen the colorectal cancer patient subset of the study for the four SNPs, with individuals with colorectal polyps as controls. Both of the latter groups are mostly Caucasian.

"Before we validate these associations in African Americans, we first need to know whether or not they exist in Caucasians - that's the number one question we want to answer," Zanetti said. "Is it possible that this is actually an African American risk factor?"

According to Zanetti, the PLCO study gives the researchers the high level of power needed to detect whether these associations really exist in Caucasians. That would then enable the team to design the rest of their study.

Zanetti noted that over the past three decades colon cancer deaths in African Americans have generally been higher than in Caucasians. "We don't know why the decline in death rates has been smaller in African Americans, but we believe it's more than one factor," she said. "These SNPs aren't necessarily the only answer. We need to keep working to uncover all the contributors to this increased risk, whether there are underlying biological issues or social determinants.

"We're doing a multitude of functional studies in the laboratory to see if we can link a phenotype to the genotype we have found," she said. "We're trying to link it to biological function - I think there's more to it than just association."

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
267-646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
213-765-4202

Cancer Tip: Study Links Breast Cancer Risk to Epigenetic Changes Related to Race, Smoking and Birth Size

registration@aacr.org () — Sun, 15 Apr 2007 12:00:00 GMT

LOS ANGELES - Women can encounter environmental factors that increase their risk of breast cancer at various periods of their physical development, beginning before birth and extending until menopause. These non-inherited, or epigenetic, changes in DNA can correlate with risk factors for breast cancer, according to research being presented at the 2007 Annual Meeting of the American Association for Cancer Research.

To study the effects of epigenetic changes in DNA, a team of researchers from Columbia University School of Public Health, led by Mary Beth B. Terry, Ph.D., collected information from former participants of the National Collaborative Perinatal Project born between 1959 and 1966.

"We've been following a birth cohort of women who were all born at Columbia in the late 50s and early 60s," said Terry. "We're interested to find if early life factors are associated with breast cancer susceptibility."

The researchers gathered data on childhood and adult exposures, along with blood samples and mammograms, from 263 women. Terry and her colleagues looked at an epigenetic effect called DNA methylation, whereby DNA is tagged by a molecular "methyl" fragment, which alters activation of the genes. In this instance, the researchers looked at global hypomethylation - aberrant methylation throughout the entirety of a person's DNA.

The researchers found differences in global DNA hypomethylation depending on breast cancer risk factors including racial group, smoking status, and infant and childhood size. "Birth size in particular has been correlated with breast cancer later in life, but nobody really knows why," Terry pointed out. "This is a small pilot study to look at one possible mechanism."

Other correlating factors included ethnic group and smoking or nonsmoking status. Twenty-one percent of whites, 39 percent of blacks, and 13 percent of Hispanics were in the highest quartile, while 35 percent current smokers were in the highest quartile compared with 15 percent former smokers and 26 percent of women who never smoked.

The researchers also plan to look at gene-specific hypermethylation in a variety of different genes that might be important for breast cancer, according to Terry.

Terry notes that although this pilot study used a very diverse sample, it was still a relatively small group, and the next step is a much larger study using samples from hundreds of women. Such an effort is currently in progress.

"We're going to try to see if we find these patterns holding up in a much larger sample now," Terry said. "We see this as a first step to understand why measures from birth might be related to adult disease much later in life."

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Premiere Cancer Organizations Partner to Reduce Disparities, Prevent Incidences

registration@aacr.org () — Sun, 15 Apr 2007 12:00:00 GMT

Susan G. Komen for the Cure Pledges More Than $2 Million to AACR

LOS ANGELES - Uniting the world's oldest and largest scientific organization dedicated to cancer research with the world's largest network of cancer survivors and activists, the American Association for Cancer Research (AACR) and Susan G. Komen for the Cure have launched a new partnership that focuses on three mutual priorities in cancer: finding ways to prevent cancer; addressing cancer disparities and ensuring ethical, standardized tissue sample storage and access for patients and researchers.

Komen for the Cure has granted more than $2 million to AACR to apply its scientific expertise and its ability to translate scientific concepts to lay-friendly language in order to build public understanding and appreciation of these three key cancer issues. Specifically, the funds will support educational outreach such as the AACR Scientist↔Survivor Program, public forums and symposia, public policy initiatives, and interactive online web destinations. The Komen pledge will also help to underwrite upcoming AACR scientific meetings, including the Frontiers in Cancer Research Prevention Meeting in Philadelphia, Dec. 5 - 8, 2007; a meeting focusing on breast cancer research; and an inaugural conference on health disparities.

AACR and Komen leaders agree that to impact cancer mortality and to increase public health, serious and sustainable progress in cancer prevention research and cancer health disparities must be made.

"While 10 million Americans are surviving cancer today due to progress in cancer research, unacceptable disparities still exist within minority communities," said AACR Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.). "Through our partnership with Susan G. Komen for the Cure, we hope to identify the challenges and eliminate the barriers preventing these populations from gaining access to knowledge about the latest advances in cancer research, treatment and prevention."

"The time is ripe to close the gaps in research and access to quality care that cause breast cancer to be deadlier for some women than others," said Susan G. Komen for the Cure President and Chief Executive Officer Hala Moddelmog. "Our partnership with AACR in combating these blatant disparities underscores Komen's commitment to prevent and ultimately end breast cancer forever. This partnership is part of our promise to invest another $1 billion in breast cancer research and community outreach programs in the next decade."

2007 is a pivotal time to enter into such a partnership as it commemorates the AACR Centennial, as well as the 25th anniversary of Susan G. Komen for the Cure. Both occasions honor the progress that has been made in cancer research and advocacy, and through this partnership, set a public course for future advances toward the prevention and cure of cancer.

Further details on this unique partnership will be announced during the opening Centennial Ceremony of the 2007 AACR Annual Meeting on Sunday, April 15th in Los Angeles, Calif.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

About Susan G. Komen for the Cure
Nancy G. Brinker promised her dying sister, Susan G. Komen, she would do everything in her power to end breast cancer forever. In 1982, that promise became Susan G. Komen for the Cure® and launched the global breast cancer movement. Today, Komen for the Cure® is the world's largest grassroots network of breast cancer survivors and activists fighting to save lives, empower people, ensure quality care for all and energize science to find the cures. Thanks to events like the Komen Race for the Cure®, we have invested nearly $1 billion to fulfill our promise, becoming the largest source of nonprofit funds dedicated to the fight against breast cancer in the world. For more information about Susan G. Komen for the Cure, breast health or breast cancer, visit www.komen.org or call 1-800 I'M AWARE.

Contact:
Jennifer Ryan
267-646-0558
ryan@aacr.org
In Los Angeles (4/13-4/19):
(213) 765-4202

Inaugural Award Honors Collaborative Team Science

registration@aacr.org () — Thu, 12 Apr 2007 12:00:00 GMT

PHILADELPHIA - Highlighting the collaborative nature of the American Association for Cancer Research (AACR), the inaugural AACR Team Science Award will be presented to a team comprised of researchers from the University of Michigan and Harvard Medical School/Brigham and Women's Hospital at the 2007 AACR Annual Meeting in Los Angeles. The award recognizes an outstanding interdisciplinary research team for its innovative science in advancing cancer research, detection, diagnosis, prevention, or treatment.

Selected for their landmark prostate cancer discovery, the team's research revealed that a majority of prostate cancers harbor recurrent gene fusions of the androgen-regulated gene TMPRSS2, with oncogenic transcription factors of the ETS family. This finding has profound clinical and biological implications for understanding prostate cancer and possibly other common solid tumors.

The AACR Team Science award, established by the AACR and generously supported by a grant from Eli Lilly and Company, acknowledges the growing importance of interdisciplinary team collaboration to the understanding of cancer and the translation of research discoveries into clinical applications.

As medical advances continue to arise, capitalizing on these new opportunities, as they apply to cancer research, often depends on the participation and contribution of researchers in other specialties including chemistry, physics, engineering, computational science, and nanotechnology. The integration of such specialties into cancer research results in the formation of interdisciplinary scientific teams.

Chosen from a pool of nearly 30 applicants, the team will collectively receive a prize of $50,000 and their institutions will be cited for their support of team science and collaboration. Winning team members are:

FROM THE UNIVERSITY OF MICHIGAN:

Scott A. Tomlins, M.D., Ph.D. Fellow, Molecular and Cellular Pathology Graduate Student
Daniel Rhodes, Ph.D., Research Investigator, Bioinformatician, M.D., Ph.D. Fellow
Rohit Mehra, M.D., Molecular Pathology Fellow, Research Investigator
Rajal Shah, M.D., Assistant Professor of Pathology, Chief of Genitourinary Pathology, Co-Director of the Prostate SPORE Tissue Core
Sooryanarayana Varambally, Ph.D. Research Assistant Professor, Cancer Biologist
Xuhong Cao, M.S., Project Manager and Research Technician
Saravana Dhanasekaran, Ph.D. Research Investigator, Molecular Biologist
John Wei, M.D., Associate Professor of Urology, Director of Clinical Outcomes Research
James Montie, M.D., Chair of Department of Urology, co-Principal Investigator of the University of Michigan Prostate SPORE
Kenneth Pienta, M.D., Professor of Internal Medicine and Urology, Principal Investigator of the University of Michigan Prostate SPORE, Medical Oncologist, and Director of the Rapid Autopsy Program
Arul M. Chinnaiyan, M.D., Ph.D., S.P. Hicks Endowed Professor of Pathology, Director, Michigan Center for Translational Pathology, co-Director of Pathology Informatics, Director of Cancer Bioinformatics, Pathologist, Principal Investigator of the University of Michigan EDRN Biomarker Development Lab., Project Investigator in the Prostate SPORE
Robin Rasor, Director of Licensing, Office of Technology Transfer

FROM HARVARD MEDICAL SCHOOL AND BRIGHAM AND WOMEN'S HOPSITAL:

Mark A. Rubin, M.D., Associate Professor of Pathology, Chief of Urologic Pathology, Co-Director Dana-Farber Harvard Prostate SPORE Tissue Core
Charles Lee, Ph.D., Assistant Professor of Pathology, Director of Cytogenetics for the Harvard Cancer Center, Associate Clinical Cytogeneticist
Sven Perner, M.D., Research Investigator, Pathology Fellow
Francesca Demichelis, PhD., Research Investigator, Computational Biologist

The AACR Team Science Award will be presented at the 2007 AACR Annual Meeting during the Centennial Ceremony on Sunday, April 16, 2007, beginning at 7:30 a.m. in Hall A of the Los Angeles Convention Center.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Jennifer Ryan
267-646-0558
ryan@aacr.org

Margaret Foti Receives Inaugural AACR Award for Leadership and Extraordinary Achievements in Cancer Research

registration@aacr.org () — Wed, 11 Apr 2007 12:00:00 GMT

PHILADELPHIA - The Board of Directors of the American Association for Cancer Research is pleased to honor Margaret Foti, Ph.D., M.D. (h.c.) with the first annual AACR Award for Leadership and Extraordinary Achievements in Cancer Research. Dr. Foti is Chief Executive Officer of the AACR; Secretary-Treasurer and Chief Executive Officer of the AACR Foundation for the Prevention and Cure of Cancer; and Managing Editor of Cancer Research, the most highly cited cancer research journal in the world.

Recognized for her extraordinary leadership of the AACR and her sustained dedication to the conquest of cancer through research, scholarly publications, communication, science education and training, and public education, the Board of Directors chose to perpetuate her leadership qualities by establishing an award in Dr. Foti's honor. Subsequent awards in her name will honor exemplary leaders in the field of cancer research.

"Dr. Foti's dedication and incredible passion for conquering cancer are well known and held in high esteem in the Association as well as globally," said Peter A. Jones, Ph.D., D.Sc., AACR past president. "Although she does not seek the limelight, preferring to let others receive recognition, the Board of Directors of the AACR is pleased to honor Dr. Foti for her leadership and achievements in cancer research."

Dr. Foti joined the AACR in 1965 as Editorial Assistant for Cancer Research, under the editorship of her first mentor, Michael B. Shimkin, M.D. She was rapidly promoted to the position of Managing Editor of the journal in 1969, becoming the youngest Managing Editor of a major scientific journal in the country.

Progressing through several key management roles in scientific publishing, Dr. Foti became the first Executive Director of the AACR in 1982. Since then, she successfully launched the next four high-quality journals of the AACR: Clinical Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; Molecular Cancer Therapeutics; and Molecular Cancer Research-all of which are prestigious publications in the cancer field, contributing over 26,000 pages to the scientific literature every year.

Seeking to bring increased innovation to the arena of scientific presentation and exchange, Dr. Foti created the AACR Special Conference series that has grown to feature more than ten special conferences a year in the U.S. and several more around the globe. She led the effort to develop the AACR Annual Meeting into the premier international cancer meeting in the world for the presentation of high-quality basic, translational, clinical and epidemiological cancer research. Under Dr. Foti's leadership, the AACR has grown to more than 25,000 members in more than 70 countries worldwide and serves tens of thousands more in the world cancer community. During her tenure, Dr. Foti has been instrumental to the success of the AACR, and in her leadership role she has strategically positioned the AACR to maximize its impact against cancer in the future.

Dr. Foti's dedication and passion for conquering cancer have already been recognized around the world as she has received many national and international awards for her contributions to cancer research, including: the Ville de Paris Award for her contributions to the field of oncology; the Cino del Duca Award for raising public awareness globally; the Community Caring Award from the William S. Graham Foundation for Melanoma Research; the American Society of Clinical Oncology Special Recognition Award for her work in advancing clinical cancer research; and most recently the Distinguished Service Award from the Association of American Cancer Institutes for her outstanding contributions to progress in cancer research. Dr. Foti has also been awarded Honorary Memberships in the Japanese Cancer Association and the European Association for Cancer Research, and an Honorary Doctorate in Medicine and Surgery from the University of Rome La Sapienza.

Among her many outside professional activities, Dr. Foti has served as a Board member, and later as President, of the National Coalition for Cancer Research; member of the Advisory Board of the Friends of Cancer Research; Board member of the Translational Genomics Institute (TGen); Medical Advisory Board Member of the Cancer Research and Prevention Foundation; member of the Council of the European Association for Cancer Research; and Board member of the Greater Philadelphia Chamber of Commerce. She has also served as President of the Council of Science Editors and of the Society for Scholarly Publishing, and has served in various capacities for the International Federation of Science Editors, the General Motors Cancer Research Foundation, the European Life Science Editors Association, the American Cancer Society, and the American Heart Association, among others. She has also been a consultant to a number of nonprofit organizations and has lectured widely at academic institutions in the United States and abroad.

The Inaugural AACR Award for Leadership and Extraordinary Achievements in Cancer Research will be presented during the Opening Centennial Ceremony of the 2007 AACR Annual Meeting, Sunday, April 15, 2007 from 7:30 a.m. to 9:00 a.m., in Hall A of the Los Angeles Convention Center.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Jennifer Ryan
267-646-0558
ryan@aacr.org

Nancy Brinker and Lance Armstrong Honored with Centennial Medals

registration@aacr.org () — Wed, 11 Apr 2007 12:00:00 GMT

PHILADELPHIA - Ambassador Nancy Brinker and Lance Armstrong will receive inaugural AACR Centennial Medals for Distinguished Public Service during special opening ceremonies of the 2007 AACR Annual Meeting. Both are being recognized for their extraordinary contributions to cancer research advocacy and awareness.

Nancy Brinker, is the founder of Susan G. Komen for the Cure, formerly the Susan G. Komen Breast Cancer Foundation. She is being recognized for her significant and sustained effort in the fight against breast cancer. Now celebrating the organization's 25th year, Ambassador Brinker's vision and leadership has led Komen to be an internationally recognized organization dedicated to eradicating breast cancer as a life-threatening disease by advancing cancer education, screening, treatment and research. Through its hugely successful Komen Race for the Cure, the foundation and its 125 affiliates have invested nearly $1 billion dollars in breast cancer research, education, screening and treatment, making Komen - aside from the federal government -- the single largest source of funds for breast cancer research and programs in the United States.

Ambassador Brinker has also been a strong advocate in the political arena, serving on the National Cancer Advisory Board, the President's Cancer Panel and the steering committee of the National Dialogue on cancer. She is also a member of the AACR's Council of Scientific Advisors.

Lance Armstrong, cancer survivor and seven-time Tour De France winner, founded the Lance Armstrong Foundation (LAF) in 1997. He is being honored for his excellence and leadership in advocacy for cancer survivors. In choosing to share with the world his personal history with cancer, he has used his influence to advocate for cancer research and survivorship, inspiring individuals to raise funds and spurring scientists toward a cure. Through the LIVESTRONG campaign with its signature yellow bracelets worn by 55 million people worldwide, LAF has raised millions of dollars and tremendously increased public awareness about cancer.

In his role as a mentor for the President's Cancer Panel, Armstrong has been an effective advocate for ensuring that cancer retains a prominent place in the national dialogue.

Both Brinker and Armstrong were chosen by the AACR Board of Directors, a distinguished panel of senior scientists, to receive this prestigious Centennial Medal and have been invited to make remarks during the Centennial Ceremony on Sunday, April 15th, beginning at 7:30 a.m.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Angela DeCicco
215-440-9300 ext. 104
decicco@aacr.org

The American Association for Cancer Research Provides Support for Promising Cancer Scientists

registration@aacr.org () — Wed, 11 Apr 2007 12:00:00 GMT

PHILADELPHIA - The American Association for Cancer Research (AACR) offers a number of grants for cancer researchers at various stages in their careers to foster the development of the most promising scientists. The AACR has newly selected 18 investigators to receive these career development awards and research fellowships, which total commitments of $1,275,000. These investigators, scientists who range in level from postdoctoral fellows to assistant professors, were selected through a rigorous and highly competitive process and will be recognized during the AACR Annual Meeting 2007, to be held April 14-18, 2007, in Los Angeles, Calif.

These awards and fellowships are part of the AACR's growing grants program. By the close of 2007, the grants program will have committed more than $5 million to outstanding cancer research projects in the U.S. and other countries around the world.

AACR-GERTRUDE B. ELION CANCER RESEARCH AWARD
The AACR-Gertrude B. Elion Cancer Research Award was established in 1993 in honor of the late Nobel Laureate Dr. Gertrude B. Elion, Scientist Emeritus at Glaxo Wellcome Co. and Past President and Honorary Member of the AACR. This award fosters meritorious basic, translational, or clinical cancer research by a tenure-track scientist at the level of assistant professor by providing a one-year grant of $50,000. It is generously sponsored by GlaxoSmithKline.
Recipient: Kent W. Christopherson II, Ph.D., Rush University Medical Center, Chicago, Ill.
Project: Umbilical Cord Wharton's Jelly Mesenchymal Stem Cell Transplant Therapies

CAREER DEVELOPMENT AWARDS
AACR Career Development Awards were first established in 1999 to provide important transitional support for direct research expenses as researchers move from the ranks of early-career scientists to faculty status.

The AACR-Genentech BioOncology Career Development Award for Cancer Research on Angiogenesis provides a two-year grant of $100,000.
Recipient: Dakun Wang, M.D., Ph.D., University of Rochester, Rochester, N.Y.
Project: Biological Function of VDU2 in pVHL-HIF-1-VEGF Pathway and Angiogenesis

The AACR-Susan G. Komen for the Cure Career Development Award for Breast Cancer Research provides a two-year grant of $100,000.
Recipient: Xiaochun Yu, M.D., Ph.D., University of Michigan, Ann Arbor, Mich.
Project: USP11, A Potential Common Regulator in Breast Tumorigenesis

The AACR-PanCAN Career Development Award for Translational Pancreatic Cancer Research, in memory of Seena Magowitz provides a two-year grant of $100,000.
Recipient: Rebekah R. White, M.D., Duke University Medical Center, New York, N.Y.
Project: Prostate Stem Cell Antigen: A Specific Target for Pancreatic Cancer Therapy

The AACR-PanCAN Career Development Award for Pancreatic Cancer Research, in honor of Carole and Bob Daly provides a two-year grant of $100,000.
Recipient: Martin E. Fernandez-Zapico, M.D., Mayo Clinic, Rochester, Minn.
Project: Characterization of the Hedgehog-Interacting Pathways in Pancreatic Cancer

The AACR-PanCAN Career Development Award for Pancreatic Cancer Research, in honor of Ralph H. Hruban, M.D. provides a two-year grant of $100,000.
Recipient: Ben Z. Stanger, M.D., Ph.D., The University of Pennsylvania, Philadelphia, Pa.
Project: Investigation of the Pancreatic "Ductome"

The AACR-PanCAN Career Development Award for Pancreatic Cancer Research, in honor of Laurie and Paul MacCaskill provides a two-year grant of $100,000.
Recipient: Kimberly A. Kelly, Ph.D., Massachusetts General Hospital, Charlestown, Mass.
Project: Molecular Imaging Agents for Early Detection of Pancreatic Cancer

The AACR-PanCAN Career Development Award for Pancreatic Cancer Research, in honor of Nancy Daly Riordan provides a two-year grant of $100,000.
Recipient: Paul J. Grippo, Ph.D., Northwestern University, Chicago, Ill.
Project: Evaluating Kras Oncogene Addiction in Pancreatic Precancer and Cancer

The AACR-PanCAN Career Development Award for Pancreatic Cancer Research provides a two-year grant of $100,000.
Recipient: Huamin Wang, M.D., Ph.D., The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Project: Functional Study of Hematopoietic Progenitor Kinase-1 in Pancreatic Cancer

RESEARCH FELLOWSHIPS
The AACR Research Fellowships were established in 1996 in response to the growing need for additional funds to train early career scientists. They are presented to postdoctoral and clinical fellows who are in their first three years of training.

The AACR-AstraZeneca-Cancer Research and Prevention Foundation Fellowship in Translational Lung Cancer Research provides a three-year grant of $90,000.
Recipient: Daniel B. Costa, M.D., Beth Israel Deaconess Medical Center, Boston, Mass.
Project: Transcription Factors in the Pathogenesis and Treatment of Lung Cancer

The AACR-Genentech BioOncology Fellowship for Cancer Research on the HER Family Pathway provides a two-year grant of $70,000.
Recipient: Elizabeth A. Mittendorf, M.D., The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Project: HER2 and Cyclin E: A Novel Interaction in Breast Cancer

The AACR-Amgen, Inc. Fellowship in Clinical/Translational Cancer Research provides a one-year grant of $40,000.
Recipient: Elizabeth C. Chao, M.D., University of California, Irvine, Calif.
Project: DASL-CRC: A Novel Assay to Identify Markers of Metastatic Recurrence

Recipient: Sao Jiralerspong, M.D., Ph.D., The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Project: The Role of LOXL2, GSK-3beta, and Snail in Invasive Breast Cancer

The AACR-MedImmune Fellowship for Research on Biologics-Based Therapies for Cancer provides a one-year grant of $40,000.
Recipient: Hoyoung Maeng, M.D., The University of Texas M. D. Anderson Cancer Center
Project: Restoration of Fas Induced Apoptosis in Cancer

The AACR-Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research provides a one-year grant of $35,000.
Recipient: Yu Chen, M.D., Ph.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Project: Targeting the Androgen Receptor via the HDAC Pathway in Prostate Cancer

The AACR-Anna D. Barker Fellowship in Basic Cancer Research provides a one-year grant of $35,000.
Recipient: Xiaoyang Wu, Ph.D., Rockefeller University, New York, N.Y.
Project: Coordinated Cytoskeletal Dynamics and Polarity: Implications in Skin Cancer

The AACR-National Brain Tumor Foundation Fellowship, in memory of Bonnie Brooks provides a one-year grant of $40,000.
Recipient: Donghong Zhao, Ph.D., City of Hope's Beckman Research Institute, Los Angeles, Calif.
Project: The Role of Hypoxia in Neural Steam Cell Migration to Glioma Cells

The AACR-PanCAN Fellowship for Pancreatic Cancer Research, in memory of Samuel Stroum provides a one-year grant of $35,000.
Recipient: Oliver A. Kent, Ph.D., Johns Hopkins University, Baltimore, Md.
Project: Analysis of MicroRNA Expression and Function in Pancreatic Cancer

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Yarissa Ortiz
267-646-0612
ortiz@aacr.org

On the Quest to Conquer Cancer, Mt. Everest

registration@aacr.org () — Wed, 11 Apr 2007 12:00:00 GMT

PHILADELPHIA -- Thin air and bone-chilling winds notwithstanding, 35-year-old Karen Brooks looked down from her perch at the world spread out below her. At 29,035 feet, Mt. Everest had a view that could only be seen from the top of the world: a curving horizon of spectacular mountain peaks and endless clouds. There, among the beauty of the Himalayas, she planted a flag bearing a photo of her mother whom she had lost to cancer. A great achievement by any standard, Brooks' triumph was two-fold: she had not only climbed the world's highest peak, but she'd raised thousands of dollars for cancer research.

After months of training and preparation, struggling against the extreme cold and facing exhaustion, hypoxia, rashes, chapped lips and hands, and even a bout with bronchitis, Brooks finally reached Everest's summit in November, 2006.

"I needed the focus, the challenge, and a way to contribute to the fight against cancer. I thought a lot about how best to do this but was drawn to Everest almost immediately," she said. "Climbing Everest is the supreme symbol of man's personal struggle to achieve. I thought such an objective was a fitting way to honor my mom."

Brooks lost her mother, Bonnie, to brain cancer in late 2003. Since then, she has channeled her sadness into a positive opportunity to raise money for cancer research, successfully raising $94,575 to date through pledges and online donations. The American Association for Cancer Research (AACR) will match her funds dollar-for-dollar to provide a grant to a postdoctoral fellow conducting brain tumor research.

The AACR-National Brain Tumor Foundation Fellowship, in memory of Bonnie Brooks, will be presented during ceremonies at the AACR's 2007 Annual Meeting on Tuesday, April 17.

Encouraged by her success on Everest, Brooks is turning her thoughts to new challenges. "I am already scheming with the fabulous Logsdon brothers (who biked from Alaska to Argentina) to climb Denali (Alaska) next year, so this is not the last you've heard of me, nor is it the last of my fundraising efforts for cancer research."

For more information about Brooks' quest to conquer cancer, visit: http://www.firstgiving.com/kbb.

Editors Note: Photographs of Brooks' "Climb to Defeat Cancer" are available for download here .

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 80 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 16,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

The National Brain Tumor Foundation (NBTF) is a non-profit health organization founded in 1981 by patients, family members, and health professionals. NBTF raises funds for research, and provides information and support to patients, their families members and friends. Since 1983, NBTF has awarded over $3 million in funding for research projects. NBTF also sponsors conferences; support groups; patient and caregiver programs including a teleconference series; a quarterly newsletter; an information nurse specialist, and a wide variety of patient information about treatments, tumor types, and coping. For more information, call 1.800.934.CURE, or visit http://www.braintumor.org.

Contact:
Yarissa Ortiz
267-646-0613
ortiz@aacr.org

AACR to Present Distinguished Public Service Awards at 2007 Annual Meeting

registration@aacr.org () — Wed, 11 Apr 2007 12:00:00 GMT

Andrew C. von Eschenbach, M.D., Harold P. Freeman, M.D., LaSalle D. Lefall, Jr., M.D. will be recognized

PHILADELPHIA - The American Association for Cancer Research will honor Andrew C. Von Eschenbach, M.D., Harold P. Freeman, M.D., and LaSalle D. Leffall, Jr., M.D., for their outstanding efforts in leadership, education and advocacy with two awards at the AACR Annual Meeting 2007.

Andrew C. von Eschenbach, M.D., will be receive the AACR Distinguished Service Award for exemplary leadership as Director of the National Cancer Institute during a time of flourishing scientific and technological advances with gradually diminishing resources. During his five-year tenure, Dr. von Eschenbach fostered new and productive interagency agreements among the U.S. Food and Drug Administration and the Centers for Medicare and Medicaid Services which streamlined the development and delivery of new medicines to seriously ill patients with cancer. His insistence upon open lines of communication and transparent governance and administration - particularly through the NCI Cancer Bulletin and other new publications - filled a vital role in keeping the public informed about the work and progress of the Institute. A nationally recognized urologic surgeon and oncologist, founding member of C-Change, former president-elect of the American Cancer Society, and three-time cancer survivor, Dr. von Eschenbach has made an impact on the fight against cancer that extends well beyond the clinical and academic communities.

Harold P. Freeman, M.D., will receive the AACR Public Service Award in recognition for his national leadership in the effort to reduce health disparities in the fight against cancer. Dr. Freeman is the founder, president, and medical director of the Ralph Lauren Center for Cancer Care and Prevention at the Memorial Sloan-Kettering Cancer Center in New York. Serving with distinction for more than a decade as the Chairman of the President's Cancer Panel, Dr. Freeman's expertise in healthcare administration has contributed enormously to raising awareness of and defining strategies to address critical healthcare issues. In addition, his pioneering research in the patient navigator concept has made significant inroads into cancer health disparity issues.

LaSalle D. Leffall, Jr., M.D., will receive the AACR Public Service Award in recognition of his leadership in the fight against cancer through excellence in teaching, research, scholarship, patient care, and public service . Dr. Leffall is the Charles R. Drew Professor at the Howard University College of Medicine in Washington, D.C. A renowned surgeon and compassionate physician, he has served as president of several major national and international organizations, including the Society of Surgical Oncologists, the American College of Surgeons, and the American Cancer Society. Through his service on the National Cancer Advisory Board, as Chairman of the President's Cancer Panel, and as Founding President and Chairman of the Board of C-Change.Dr. Leffall has received numerous awards and honors for his contributions to the national campaign for cancer awareness.

The AACR Public Service Award and the AACR Distinguished Service Award will be presented at 7:00 a.m. Sunday, April 15, during opening ceremonies of the 2007 AACR Annual Meeting. Members of the media registered for the meeting are welcome to attend.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Angela DeCicco
215-440-9300 ext. 104
decicco@aacr.org

Aflac Expands Decade-Long Partnership with AACR

registration@aacr.org () — Wed, 11 Apr 2007 12:00:00 GMT

Awards Support Young Investigators, Pediatric Cancer Research

PHILADELPHIA -- Recognizing the growing need to nurture the next generation of cancer researchers, Aflac, a leading provider of insurance products, has expanded its generous commitment to the American Association for Cancer Research by sponsoring the new AACR-Aflac Career Development Award for Pediatric Cancer Research, in addition to renewing its support for the AACR Associate Member Council and the AACR-Aflac Scholar-in-Training Awards, now in their 10th year.

At the heart of Aflac's corporate mission and philanthropy is support for pediatric cancer. The AACR-Aflac Career Development Award for Pediatric Cancer speaks to this mission by providing four young investigators with research funding as they seek to establish a name for themselves in the field of pediatric cancer research.

Likewise, the Scholar-in-Training Awards enhance the education of early-career scientists by providing financial support to attend AACR Annual Meetings. Attended by more than 17,000 scientists from around the globe, the AACR Annual Meeting enables young investigators to present research, learn from various educational sessions and symposia, and take advantage of mentorship and networking opportunities.

"We are so grateful to Aflac for their continued support of promising young cancer researchers," said AACR Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.). "Not only do these awards provide a vital foundation for those just starting out in their careers, but they also help retain in cancer research some of the brightest scientists who might otherwise pursue careers in other areas of science."

During a year of noteworthy anniversaries, Aflac increased their support in 2007 to mark its decade-long partnership with AACR, as well as the AACR Centennial. Commemorating 100 years of progress in cancer research, in 2007 the AACR honors past achievements and looks to foster future advancements in the fight against cancer.

"Providing scholarship and training awards toward cancer treatment and research is a part of Aflac's commitment to help stamp out the disease," said Buffy Swinehart, Aflac's Manager of Philanthropy and Cause Related Marketing. "AACR highlights the best and brightest individuals to help make this possible and we are delighted to continue honoring those scientists who have committed their works to this great effort."

Since 1997, more than 721 AACR-Aflac Scholar-in-Training Awards have been presented to AACR Associate Members, with an overwhelming number of these recipients remaining in the cancer research field and successfully moving ahead to the next stages of their careers. As part of Aflac's 10th anniversary celebration, a special alumni event will be held during the AACR Annual Meeting on Monday, April 16, 2007, to reunite these young minds and marvel at their progress.

One such success story is Heather Cunliffe, Ph.D., a 2001 recipient of the AACR-Aflac Scholar-in-Training Award. Dr. Cunliffe is currently an investigator and head of the breast cancer research unit at the Translational Genomics Research Institute in Phoenix, Ariz.

"Receiving the AACR-Aflac Award played an important role in my progress, as it allowed me to travel and present at the AACR-NCI-EORTC Meeting, where I met my now primary collaborator," Cunliffe explained. "I am grateful to AACR and Aflac for their support, as it is likely that I would not have begun this fruitful collaboration without the necessary funding to attend this meeting."

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

About Aflac
For more than 50 years, Aflac products have given policyholders the opportunity to direct cash where it is needed most when a life-interrupting medical event causes financial challenges. Aflac is the number one provider of guaranteed-renewable insurance in the United States and the number one insurance company in terms of individual insurance policies in force in Japan. Our insurance products provide protection to more than 40 million people worldwide. Aflac has been included in Fortune magazine's listing of America's Most Admired Companies for six consecutive years and in Fortune magazine's list of the 100 Best Companies to Work For in America for nine consecutive years. Aflac has also been recognized three times by both Fortune magazine's listing of the Top 50 Employers for Minorities and Working Mother magazine's listing of the 100 Best Companies for Working Mothers. Aflac Incorporated is a Fortune 500 company listed on the New York Stock Exchange under the symbol AFL. To find out more about Aflac, visit aflac.com.

Contact:
Jennifer Ryan
267-646-0558
ryan@aacr.org

American Association for Cancer Research Annual Meeting Showcases Significant Developments in Understanding and Targeting Cancers

registration@aacr.org () — Tue, 10 Apr 2007 12:00:00 GMT

LOS ANGELES - Data demonstrating genetic differences in individuals' susceptibility to certain cancers as well as differences in how people respond to specific cancer treatments will take center stage when more than 17,000 scientists from around the world gather at the Los Angeles Convention Center April 14-18 for the 2007 Annual Meeting of the American Association for Cancer Research (AACR). Key data presented at the meeting will also include findings related to the safety and effectiveness of several new, high-profile cancer therapies and vaccines.

"Because of significant diagnostic and therapeutic advances such as personalized and targeted therapies that prolong patients' lives, the number of people successfully managing and living with cancer continues to grow," said Geoffrey M. Wahl, Ph.D., President, AACR. "By hosting the largest meeting in the world of its kind - where the science behind these significant developments is shared and analyzed by researchers at the leading edge of cancer study - the AACR promotes clinical exchange with the goal of ensuring research discoveries translate directly into improved patient outcomes."

The theme of this year's annual meeting, "A Century of Leadership in Science - A Future of Cancer Prevention and Cures," commemorates the AACR's Centennial and underscores the remarkable scientific advances that researchers have achieved in the 100 years since the organization's founding, well as the critical importance of ongoing research.

The opening Centennial Ceremony will set an exciting and inspirational tone for a week of science and discovery, with a procession of young researchers bearing flags of all 70 AACR member nations, appearances by the University of Southern California (USC) Marching Band, the All-American Boys' Choir and presentation of Centennial Medals and other honors to leading cancer researchers and advocates.

The opening plenary, "Translating a Century of Science into a Future of Cancer Prevention and Cures" - featuring world leaders in the fields of cancer genetics, cellular metabolism, stem cell biology, molecular diagnostics, targeted therapies, early detection and the impact of future cancer science on public health - will provide a vantage point for historical and current perspectives across the spectrum of basic and applied cancer science.
Late-breaking plenary sessions in basic, translational and clinical cancer research will cover the latest advances from the laboratory and their translational potential to the clinic. Special sessions will also feature phase I and phase II studies of novel therapeutic agents in early-stage clinical trials, as well as the latest phase III clinical trial findings.

"This meeting provides an unmatched opportunity to exchange information on current and emerging discoveries, forge new collaborations and identify future opportunities in virtually all areas of modern cancer research and patient care," said Ronald A. DePinho, M.D., scientific chairperson of the 2007 AACR Program Committee. "In our Centennial year, this deeply reflects the intent of our founders on a scale that they could scarcely imagine."

AACR's Annual Meeting attracts attendees including leading academic, industry and government scientists, as well as clinical oncologists, students, cancer survivors, advocates and other health care professionals. Such a diverse group facilitates a cross-disciplinary exchange of new ideas and collaborations. This year, more than 6,000 abstracts were submitted for presentation, complementing an outstanding program of scientific and educational events.

Among meeting highlights, the AACR has selected more than 35 scientific abstracts for presentation by their authors in 10 press briefings, each highlighting a critical or emerging area of cancer research. Featured press briefing topics include:

The role of genetics in increasing susceptibility to certain cancers and decreasing positive outcomes among African Americans

Clinical data illustrating the impact of the HPV-16/18 LI VLP AS04 candidate vaccine on precancerous lesions and the human papillomavirus

Studies demonstrating the protective effects of certain vegetables, fruits and tea against ovarian, pancreatic and breast cancers

Late-breaking findings from studies of cetuximab in people with chemotherapy-refractory colorectal cancer

Additional briefings will focus on the latest research in patient prognosis, personalized medicine, inflammation, cancer biomarkers, stem cells and cancer diagnosis.

With the aim of inspiring the next generation of young cancer researchers, the AACR has invited nearly 300 local high school students to participate in "The Conquest of Cancer and the Next Generation," a day-long program on the floor of the AACR meeting that will feature educational lectures and a tour of poster displays and exhibits as well as a networking reception. Many of these high school students will be paired with mentors among the AACR membership for guidance and education.

"Over the last 100 years, the AACR has been privileged to be an integral part of the scientific discussion surrounding cancer," said William N. Hait, M.D., Ph.D., President-Elect, AACR. "It is critical that we maintain our commitment not only to providing a venue for research and collaboration but also to stimulating the achievement of the cancer scientists of the future."

Reporters and Editors: For more information or to register for the 2007 Annual Meeting of the AACR, please call 215-440-9300, email communications@aacr.org, or visit www.aacr.org.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact:
Staci Vernick Goldberg
(267) 646-0616
goldberg@aacr.org
In Los Angeles (4/12-4/18):
(213) 765-4202

Leading Researchers Honored for Progress in Cancer Prevention, Detection and Treatment

registration@aacr.org () — Tue, 03 Apr 2007 12:00:00 GMT

AACR Presents Research Achievement Awards at 2007 Annual Meeting

PHILADELPHIA - World-class cancer researchers whose science has significantly contributed to progress in the fight against cancer will be recognized April 14-18, 2007, by the American Association for Cancer Research (AACR) at its 2007 Annual Meeting in Los Angeles, Calif.

A series of awards given annually by the AACR, the world's oldest and largest professional organization representing cancer scientists from the United States and nearly 70 other countries, honor outstanding accomplishments in basic research, clinical care, therapeutics and prevention. Each recipient presents an educational lecture at the AACR Annual Meeting.

"During this, our Centennial year, we are privileged to recognize some of the many dedicated scientists, nominated by their peers, whose extraordinary work has helped to shape the direction of cancer research," said AACR Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.).

"As we commemorate 100 years of progress in cancer research, we look to these individuals as research leaders in our shared mission to conquer cancer," Foti added.

Peers and colleagues nominate award candidates. Selection committees for each award, comprised of leaders in all areas of cancer research, choose the honorees.

This year's winners are a diverse group of cancer researchers from around the country who exemplify the theme of the 2007 Annual Meeting, "A Century of Leadership in Science, A Future of Cancer Prevention and Cures." The honorees are:

Janet S. Butel, Ph.D., The Joseph L. Melnick Professor of Virology; Program Leader, Dan L. Duncan Cancer Center; Director, Baylor-UT Houston Center for AIDS Research; and Distinguished Service Professor and Chair, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, will be honored with the 10th Annual AACR-Women in Cancer Research-Charlotte Friend Memorial Lectureship, for her fundamental contributions to the biology of tumor viruses, their oncogenic mechanisms, and their importance in the infectious etiology of cancer. The Women in Cancer Research Council of the AACR established this lectureship in 1998 to honor renowned virologist and discoverer of the Friend virus, Dr. Charlotte Friend. The lecture recognizes an outstanding scientist who has made meritorious contributions to the field of cancer research and who has, through leadership or by example, furthered the advancement of women in science. Butel will present her lecture, "Polyomavirus SV40: insights into viral carcinogenesis," at 5:45 p.m. on Saturday, April 14, in Hall B of the Los Angeles Convention Center.

Harold P. Freeman, M.D., Professor of Clinical Surgery at Columbia University College of Physicians and Surgeons and President, Founder, and Medical Director of the Ralph Lauren Center for Cancer Care and Prevention in New York, is the recipient of the second annual AACR-Minorities in Cancer Research-Jane Cooke Wright Lectureship, for his innovative work on the Patient Navigator Program, a community-based strategy to reduce cancer disparities; for his patient-focused programs in breast and cervical cancer screening in a public hospital; for translating hospital cancer care to the community; and for raising awareness of the economic, social, and racial injustices related to health disparities through his scholarship. The award, sponsored by the AACR-Minorities in Cancer Research Council, is named in honor of Jane Cooke Wright, M.D., an African-American woman pioneer in clinical cancer chemotherapy and an exceptional scientist. Dr. Freeman's lecture will take place at 4:15 p.m. on Sunday, April 15, 2007 in Hall B of the Los Angeles Convention Center.

Alexander Varshavsky, Ph.D., Howard and Gwen Laurie Smits Professor of Cell Biology at the California Institute of Technology, is the recipient of the third Annual AACR-Irving Weinstein Foundation Distinguished Lectureship. He is awarded this year's lectureship for his discovery of biological regulation by intracellular protein degradation and its central role in cell function and activity. His fundamental research, conducted in the 1980s, has revealed the biological significance and specific functions of the ubiquitin system, including its roles in the cell cycle, DNA repair, transcription, protein synthesis, and stress responses. This seminal advance, made through a set of interconnected discoveries, has spawned a central theme of modern biomedical science and led to a fundamental understanding of cancer. Named in honor of the late Irving Weinstein, AACR and the Irving Weinstein Foundation created the distinguished lectureship in 2005 to recognize the accomplishments of an individual whose innovations in science and position as a thought leader have inspired creativity and new directions in cancer research. Varshavsky will present his lecture titled, "The Ubiquitin System and the N-End Rule Pathway," at 1:30 p.m. on Monday, April 16, 2007 in Hall A of the Los Angeles Convention Center.

Michael B. Kastan, M.D., Ph.D., Cancer Center Director, St. Jude's Children's Research Hospital, Memphis, Tenn., will receive the 47th Annual AACR-G.H.A. Clowes Memorial Award for his leadership in ground-breaking studies of cellular responses to DNA damage. The AACR and Eli Lilly and Company established this award in 1961 to honor Dr. G.H.A. Clowes, a founding member of the AACR and a research director at Eli Lilly. The oldest award given by AACR, this honor recognizes an individual with outstanding recent accomplishments in basic cancer research. Dr. Kastan's lecture, "DNA damage responses: mechanisms and implications for human disease," will take place at 8:00 a.m. on Tuesday, April 17, in Hall A of the Los Angeles Convention Center.

Daniel A. Haber, M.D., Ph.D., Director, Massachusetts General Hospital Cancer Center, and Laurel Schwartz Professor of Oncology, Harvard Medical School, Boston, Mass., will be awarded with the 31st Annual AACR-Richard and Hinda Rosenthal Foundation Award. Designed to provide incentive to young investigators relatively early in their careers, the award was established in 1977 by AACR and the Rosenthal Foundation to recognize research that has made, or promises to make, a notable contribution to improved clinical care in the field of cancer. Dr. Haber, who is honored for his contributions to the understanding of the molecular basis of cancer and applying these insights to the use of targeted therapies for cancer, will give his lecture "Targeting Genetic Lesions in Cancer: Lessons from EGFR and MET," at noon on Tuesday, April 17, in Hall A of the Los Angeles Convention Center.

Thomas W. Kensler, Ph.D., Professor in the Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD., will receive the 16th Annual AACR-American Cancer Society Award for Research Excellence in Cancer Epidemiology and Prevention. Established in 1992, the award recognizes outstanding research accomplishments in the fields of cancer epidemiology, biomarkers and prevention. Honored for developing translational strategies using a variety of chemopreventative compounds for targeting reduction of liver cancer in the economically developing world, Kensler will present his lecture on "Translating molecular targets for chemoprevention into interventions for at-risk populations" at 2:15 p.m. on Tuesday, April 17, in Hall A of the Los Angeles Convention Center.

Kenneth C. Anderson, M.D., Kraft Family Professor of Medicine, Harvard Medical School; Chief, Division of Hematologic Neoplasia, Director, Jerome Lipper Multiple Myeloma Center and Vice Chair of the Program in Transfusion Medicine, Department of Medical Oncology at Dana Farber Cancer Institute, Boston, Mass., will be honored for his contributions to translational and clinical advances in multiple myeloma. Dr. Anderson will receive the 12th Annual AACR-Joseph H. Burchenal Memorial Award for Outstanding Achievements in Clinical Research and present his lecture, "Oncogenomics to target the tumor cell in its microenvironment," at 5:30 p.m. on Tuesday, April 17, in Hall A of the Los Angeles Convention Center. The award was established in 1996 to recognize outstanding achievements in clinical cancer research and honors the late Dr. Joseph Burchenal, Honorary Member and Past President of the AACR, and a major figure in clinical cancer research.

Kornelia Polyak, M.D., Ph.D., Associate Professor of Medicine in the Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass., will receive the 27th Annual AACR Award for Outstanding Achievement in Cancer Research, in recognition of her innovative contributions to understanding molecular alterations in breast cancer. The AACR established this award in 1979 to recognize a young investigator for meritorious achievements in cancer research. Dr. Polyak's lecture, "Breast tumor progression: the role of stem cells and the microenvironment," will take place at 8:00 a.m. on Wednesday, April 18, in Hall A of the Los Angeles Convention Center.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Jennifer Ryan
267-646-0558
ryan@aacr.org

World-Renowned Chemist Honored with Inaugural Lectureship

registration@aacr.org () — Tue, 03 Apr 2007 12:00:00 GMT

PHILADELPHIA - Samuel J. Danishefsky, Ph.D., is the recipient of the First Annual AACR-CICR Award for Outstanding Achievement in Chemistry in Cancer Research. The award honors novel and significant chemistry research which has led to important contributions to the field of cancer research. Danishefsky is the Kettering Chair and Director of the Laboratory for Bioorganic Chemistry at Memorial Sloan-Kettering Cancer Center, and a professor of Chemistry at Columbia University.

Regarded as one of the world's leading chemists, Danishefsky specializes in the synthesis of complex, biologically active organic molecules. For more than 40 years, his work has provided major fundamental advances in the methodology and logic of organic synthesis, and offered a tremendous body of research in organic chemistry impacting both the strategy and technology of synthesis. Danishefsky's work is unique in bringing the triumphs of organic chemistry to the treatment of cancer and his research has literally moved compounds from conception through laboratory synthesis, preclinical evaluation and into clinical trials.

His modified epothilones (a new class of cytotoxic molecules) are currently in Phase I and Phase II breast cancer clinical trials. He also discovered fludelones, a remarkable class of compounds which show promise for broad therapeutic indications. Another major area of research of Danishefsky involves his advances directed to fully synthetic anticancer vaccines, which are in various stages of pre-clinical and clinical development.

Danishefsky earned his undergraduate degree from Yeshiva University and his Ph.D. in chemistry from Harvard University. He is currently a Professor of Chemistry at Columbia University and the Kettering Director of Bioorganic Chemistry at Memorial Sloan-Kettering Cancer Center.

A celebrated researcher, Danishefsky was elected to the National Academy of Sciences in 1986 and received its Award in Chemical Sciences in 2006. His many awards include the Wolf Prize in Chemistry in 1996; the ACS Cope Medal in 1998; the Bristol Myers Squibb Lifetime Achievement Award in 2006; the Benjamin Franklin Award in 2006; and the ACS Roger Adams Award in Organic Chemistry in 2007.

Danishefsky will present his lecture titled, "Connectivity between the power of chemical synthesis and exciting possibilities in oncology," during the AACR Annual Meeting in Los Angeles, Calif. The lecture will take place at 5:30 p.m. on Sunday, April 15, 2007 in Hall B of the Los Angeles Convention Center.

The AACR-CICR Award for Outstanding Achievement in Cancer Research Lectureship was established in 2007 by the AACR's Chemistry in Cancer Research Working Group, through the support of GlaxoSmithKline.

Editors Note: To further information on this lectureship, please visit www.aacr.org.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Jennifer Ryan
267-646-0558
ryan@aacr.org

AACR Establishes New Lecture in Honor of Princess Takamatsu

registration@aacr.org () — Tue, 03 Apr 2007 12:00:00 GMT

Webster K. Cavenee to Present Lecture at Annual Meeting

PHILADELPHIA - The American Association for Cancer Research (AACR) will honor Webster K. Cavenee, Ph.D, recipient of AACR Princess Takamatsu Memorial Lectureship at the 2007 Annual Meeting, to be held April 14-18 in Los Angeles, Calif.

The Lectureship was established in honor of the late Princess Takamatsu of Japan and is supported by the Princess Takamatsu Cancer Research Fund. Cavenee is being recognized for his groundbreaking discoveries regarding the genetic mechanisms of predisposition to human cancer and his commitment to the international cancer community.

Cavenee's original research seeking to define the genetic lesions in retinoblastoma provided the first genetic evidence for the existence of tumor suppressor genes, one of the most influential breakthroughs in cancer research. This breakthrough confirmed the "two-hit hypothesis," fundamentally altering the way scientists think about the onset of cancer and its progression.

Cavenee is the director of the Ludwig Institute for Cancer Research, San Diego Branch. In 2004, the University of California, San Diego named him Distinguished Professor.

Princess Takamatsu became involved in cancer research following the death of her mother from bowel cancer in 1933. In 1968, she established the Princess Takamatsu Cancer Research Fund, a trust that allocates public monies to innovative cancer research. Through her various activities, the Princess promoted the importance of collaborations across scientific disciplines and among scientists across the globe.

Cavenee's inaugural lecture, Targeting Defective Receptors in Human Brain Cancer: Mechanisms and Therapeutic Opportunities, will take place at 1 p.m. on April 17, in Hall A of the Los Angeles Convention Center. All media registered for the meeting are welcome to attend.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Angela DeCicco
215-440-9300 ext. 104
decicco@aacr.org

Donald Metcalf Receives American Association for Cancer Research Lifetime Achievement Award

registration@aacr.org () — Mon, 02 Apr 2007 12:00:00 GMT

PHILADELPHIA - Donald Metcalf, M.D., the physiologist renowned as "the father of hematopoietic cytokines" for his pioneering work on the control of blood cell formation, will receive the American Association for Cancer Research Award for Lifetime Achievement in Cancer Research.

The award will be presented on Monday, April 16, 2007 during ceremonies at the AACR's Annual Meeting in Los Angeles, Calif.

In early studies, Dr. Metcalf discovered the function of the thymus gland in controlling the formation of lymphocytes, and beginning in 1965, co-developed a series of specialized culture techniques permitting the growth of various types of blood cells. These cultures led him and his team to the discovery of "colony-stimulating factors" (CSFs), hormones that control white blood cell formation and are, therefore, responsible for one's resistance to infection. His work, with that of others, led to the successful cloning of the genes for all mouse and human CSFs, and the mass production of these hormones by bacterial, yeast, and other cells for therapeutic use.

Dr. Metcalf's work provided the pivotal demonstration that CSFs, when injected into animals, stimulated the formation and regulated the activity of white blood cells. Exploiting this, his collaborators documented the effectiveness of GM-CSF and G-CSF (two primary white blood cell regulators) when injected into patients. These blood cell regulators have been in extensive clinical use since 1988 in the management of cancer patients following the use of chemotherapy or radiation therapy. CSF treatment accelerates hematopoietic regeneration in these patients, reducing the risk of infections, usefully shortening time of hospitalization, and permitting the delivery of increased doses of chemotherapy.

Furthermore, Dr. Metcalf and his colleagues showed that CSFs could elevate the levels of hematopoietic stem cells in the blood equivalent to levels in bone marrow. Not only was pheresis of peripheral blood a less traumatic and more prolific source of cells for transplantation, but the CSF-elicited stem cells achieved a more rapid recovery of white cell and platelet levels in patients. This dramatic advance has largely replaced bone marrow transplantation in cancer treatment and has had a major impact on the manner in which chemotherapy is used in cancer patients.

"As a world-renowned scientist and leader in the cancer research community, Dr. Metcalf is an outstanding choice for the AACR Award for Lifetime Achievement in Cancer Research," said Margaret Foti, Ph.D., M.D. (h.c.), AACR chief executive officer. "Dr. Metcalf's contributions to the field of hematology research have not only had a major impact in cancer research, but have also revolutionized our understanding of many other blood diseases.

Dr. Metcalf is the Carden Fellow in Cancer Research at the Walter and Eliza Hall Institute and Professor Emeritus, University of Melbourne, Australia. He received his B.Sc. in Virology (1951), his M.B.B.S. (1953), and his M.D. (1961) from the University of Sydney, Australia.

Dr. Metcalf has received numerous awards including the Albert Lasker Award, the Bristol-Myers Award, the Armand Hammer Prize, the Sloan Prize, and many others. In his native country, he has received the Gold Medal from the Australian Cancer Society, the Burnet Medal from the Australian Academy of Science, and the Prime Minister's Prize for Science, among others. In addition, he has been named an Officer and a Companion of the Order of Australia.

The AACR Award for Lifetime Achievement in Cancer Research was established and first presented in 2004 to honor an individual who has made significant fundamental contributions to cancer research, either through a single scientific discovery or a body of work. These contributions, whether they have been in research, leadership, or mentorship, must have had a lasting impact on the cancer field and must have demonstrated a lifetime commitment to progress against cancer.

Editors Note: To download a high-resolution photograph of Dr. Metcalf and for further information on this lectureship, please e-mail ortiz@aacr.org.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

AACR Awards Minority and Other Underrepresented Scientists

registration@aacr.org () — Fri, 30 Mar 2007 12:00:00 GMT

61 Receive Scholar Awards to Participate in American Association for Cancer Research Annual Meeting in Los Angeles, Calif., April 14-18, 2007

PHILADELPHIA - Three Scholar Awards programs, sponsored by the American Association for Cancer Research, will provide scientists traditionally underrepresented in cancer research with financial support to participate in the premier international meeting in the field. At the 2007 AACR Annual Meeting, more than 17,000 clinical oncologists, basic scientists, epidemiologists and translational researchers from around the world will discuss the latest findings and most significant information in laboratory, translational and clinical cancer research. More than 6,000 scientific abstracts will be presented this year.

"The AACR maintains a strong commitment to enhancing the educational and training opportunities available to the next generation of cancer researchers," said Margaret Foti, Ph.D., M.D. (h.c.), AACR's chief executive officer.

"Our primary mission is to promote the exchange of knowledge and new ideas among the scientists on the front lines in the quest for the prevention and cure of cancer," Foti added. "These awards seek to improve the inclusiveness of cancer research, so that no pool of potential talent goes untapped."

26 early-career scientists will receive AACR Minority Scholar in Cancer Research Awards to participate in the 2007 AACR Annual Meeting. These awardees were selected on the basis of their scientific qualifications, references from mentors, and an estimation of the potential professional benefit to the awardees. During the meeting they will attend scientific sessions, participate in networking events, and present meritorious scientific papers.

Criteria for candidacy for this award program include the stipulation that the applicant fit the National Cancer Institute definition of groups traditionally underrepresented in cancer and biomedical research: African Americans, Alaskan Natives, Hispanics, Native Americans, and Native Pacific Islanders. Additionally, eligible candidates must be full-time graduate or medical students, residents, clinical or postdoctoral fellows, or junior faculty members. The award will provide complimentary registration, travel expenses, and a subsistence stipend to participate in the Annual Meeting and AACR Special Conferences.

The Minority Scholar Awards are supported generously by grants from the Comprehensive Minority Biomedical Branch of the National Cancer Institute.

The AACR Minority-Serving Institution Faculty Scholar in Cancer Research Awards aim to increase the scientific knowledge base of faculty members at Minority-Serving Institutions, encourage their research, and assist to inspire their students to pursue careers in cancer research. Formerly known as the AACR-Historically Black Colleges and Universities Faculty Scholar Awards, the program has been expanded to include predominantly Hispanic-Serving Institutions and Tribal Colleges and Universities to extend its reach. These awards also are supported by grants from the National Cancer Institute's Comprehensive Minority Biomedical Branch.

Candidates must have completed doctoral studies or clinical fellowships relevant to cancer research and hold full-time faculty positions at the level of assistant professor or above at an institution designated as minority-serving. They must also be engaged in meritorious basic, clinical or translational cancer research. Each of the 25 AACR-MSI Faculty Scholars chosen this year will receive financial support toward expenses associated with attending the AACR Annual Meeting.

A committee of the AACR Minorities in Cancer Research Council administers both of these award programs.

AACR-Women in Cancer Research Brigid G. Leventhal Scholars in Cancer Research Awards honor members of AACR-Women in Cancer Research who are scientists-in-training and first authors of meritorious scientific papers selected for presentation at the AACR Annual Meeting. They are full-time graduate students, medical students, residents, clinical fellows or the equivalent, or postdoctoral fellows. The awards are named for Dr. Brigid Gray Leventhal, who began her career in pediatric oncology at the National Cancer Institute, conducting clinical and laboratory research on leukemia and other childhood cancers. Subsequently, she served on the faculty of the Johns Hopkins University School of Medicine, until her own life was claimed by cancer in 1994.

There are 10 AACR-WICR Brigid G. Leventhal Scholars in 2007. The WICR Council sponsors the awards with the generous support of a grant from AstraZeneca.

Editors Note: The names, affiliations and, where applicable, abstract titles of all Scholar Award winners' research projects are available for download here, or on the AACR website.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

The Next Generation of Cancer Researchers

registration@aacr.org () — Fri, 30 Mar 2007 12:00:00 GMT

AACR Annual Meeting Engages High School Scientists

PHILADELPHIA -- It is never too early to start thinking about what you want to be when you grow up, especially if you want to be a cancer researcher. The American Association for Cancer Research (AACR) is capturing the interest of aspiring young scientists during a special program for high school students at the Annual Meeting 2007, April 14-18, in Los Angeles, Calif.

Nearly 300 high school students from the Los Angeles area will participate in "The Conquest of Cancer and the Next Generation," a day-long program filled with inspiring educational lectures, a tour of poster displays and exhibits, and a networking reception.

"The field of cancer research in the U.S. is at risk of losing bright young minds because of decreasing research funds, resulting in heightened competition and relocation of young researchers to other countries," said AACR Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.). "AACR is hoping to reduce that risk and re-gain our competitive edge by nurturing young high school students who show promise for the future of cancer research."

The program begins with a series of educational sessions including: "Understanding Cancer," "Keys to Cancer Prevention" and "Why Cancer Research Needs You," led by some of the nation's top cancer researchers. Students will also hear from a cancer survivor and advocate on the importance of cancer research.

Each student will then be matched with a mentor from the AACR membership who will guide students through the poster presentation area to explain scientific displays describing the causes, diagnosis, treatment and prevention of cancer, and navigate the exhibit hall to learn about the latest products and services for laboratory and clinical research.

A networking reception concludes the program where students will participate in an "Ask the Experts" session and meet one-on-one with leading scientists to answer questions about various areas of cancer research. Students will also have the opportunity to present their own posters and tabletop exhibitions of school projects and learn about job opportunities and summer internships. Program participants are encouraged to stay in touch with their mentors for continued guidance, encouragement and career advice.

AACR's special program for high school students is held each year at the Annual Meeting, traveling to various cities across the country and reaching out to a wide variety of promising, young students. For more information on this unique program, visit www.aacr.org.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Jennifer Ryan
267-646-0558
ryan@aacr.org

AACR-Bardos Awards for Undergraduate Students Announced

registration@aacr.org () — Fri, 30 Mar 2007 12:00:00 GMT

PHILADELPHIA - To foster interest in cancer research careers among the next generation of young scientists, the AACR will provide an opportunity for undergraduate students to experience the field first hand at its Annual Meeting 2007 through the AACR-Thomas J. Bardos Science Education Awards for Undergraduate Students.

This program is designed to enhance the education of the students by providing financial support to attend AACR Annual Meetings, which are attended by more than 17,000 scientists from around the globe. The AACR Annual Meeting allows young investigators to present research, learn from various educational sessions and symposia, and take advantage of mentorship and networking opportunities.

The award program is open to full-time, third-year undergraduate students majoring in science. In addition, winners will participate in the 2007 Undergraduate Student Caucus and Poster Competition. Because the award provides registration for two consecutive meetings, 10 winners will attend the Annual Meeting 2008 as well.

Bardos, a native of Hungary, has been an AACR member for nearly 50 years and, since 1997, has supported the Science Education Awards for college students. Following World War II, he came to the United States, earning a Ph.D. in chemistry from the University of Notre Dame. He went on to hold a full professorship at the State University of New York at Buffalo, where he was a member of the faculty until his retirement in 1995; he now holds emeritus status. Contributions are matched by the AACR to support these awards.

The AACR Annual Meeting 2007 will be held April 14-18 at the Los Angeles Convention Center. The Undergraduate Student Caucus will be held at 12:00 p.m. on Sunday, April 15. Programs for young scientists are organized by the AACR Science Education Committee.

For a list of winners or further information on the Undergraduate Student Caucus, please e-mail decicco@aacr.org or visit the AACR website at www.aacr.org.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Angela DeCicco
215-440-9300 ext. 104
decicco@aacr.org

Pezcoller Foundation-AACR Recognizes the Outstanding Achievements of Mina J. Bissell

registration@aacr.org () — Tue, 27 Mar 2007 12:00:00 GMT

Bissell Honored for Pioneering Work in Understanding the Role of the Tumor Microenvironment and Three-dimensional Architecture in Cell and Cancer Biology

PHILADELPHIA - Mina J. Bissell, Ph.D., is the recipient of the 2007 Pezcoller Foundation-AACR International Award for Cancer Research for her pioneering work on the relationship between cancer genetics and the three-dimensional structure of cells and tissues. Bissell is Distinguished Scientist in the Life Sciences Division at Lawrence Berkeley National Laboratory and a recognized leader in the study of the extracellular matrix (ECM) - the complex physical and biochemical environment that surrounds living tissues - and how it regulates genes in both normal organs and malignant tumors.

"Dr. Bissell is an extraordinarily accomplished cell biologist whose discoveries have had an enormous impact on our understanding of the mechanisms by which living cells proliferate, differentiate, become cancerous, or, ultimately, die," said AACR Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.). "Her insights into the role of the extracellular matrix in gene expression have revolutionized our fundamental understanding of cancer biology."

This year marks the tenth anniversary of the award, which recognizes an individual who has made a major scientific discovery in basic or translational cancer research. Bissell will give an award lecture at the AACR Annual Meeting 2007 in Los Angeles, Calif., April 14-18. Her talk, entitled "Phenotype Overrides Genotype in Normal Mammary Gland and Breast Cancer," will be given at 5:30 p.m., Sunday, April 15, in Hall A of the Los Angeles Convention Center.

In Bissell's honor, the Pezcoller Foundation will hold an award ceremony in early May in Trento, Italy, where she will receive a cash award of €75,000 and a medallion.

"I am honored to be the recipient of this prestigious award, and I thank the selection committee as well as the past and present members of my group for their hard work and vision" said Bissell.

Bissell's work in the last two decades has brought the research community to a closer understanding of how cells function in three-dimensional living tissue as opposed to the two-dimensional culture dish. Her group continues to do pioneering work in this area, and in a recent article in Science her group described a new assay using micropatterns of cells sandwiched between two layers of ECM gels, and showed how mammary cells regulate branching which could be used to understand how breast cancer cells become invasive.

The citation for the Pezcoller Foundation-AACR award points out how for over three decades, Bissell's elegant studies have revealed that the critical unit of biological function is the integrated signaling circuit provided by the tissue (organ) architecture. She is being honored for systematically looking beyond the single cell, showing that the interaction of cells with each other and with the ECM and the rest of the microenvironment influence cell proliferation, survival, morphogenesis, differentiation, and cell fate, all processes that go awry in cancer. These studies are innovative and the approaches imaginative, combined with rigor and persistence. The concepts she has developed are fundamental to normal tissue morphogenesis and cancer, and the impact of her work is profound for how we view biological regulation. In short, Bissell has taken an original and refreshing approach that has produced revolutionary new concepts.

Bissell received her Bachelor's degree in chemistry with honors from Radcliffe/Harvard College. She received her Ph.D. in microbiology/molecular genetics from Harvard University. She began her career as a Milton Fellow at Harvard University in 1969, subsequently serving as an American Cancer Society Fellow at UCB. In 1972 she joined the Staff of Lawrence Berkeley National Laboratory becoming a Senior Scientist in 1976. She served as the Director of the Cell and Molecular Biology Division from 1988-1992; as the Director of all Life Sciences from 1992-2002; as the Associate Director of Biosciences from 1995-2002; and upon stepping down as Director, was named Distinguished Scientist and Senior Advisor to the Laboratory Director on Biology in 2002, positions she currently holds.

Bissell also serves as a member of the faculty of three graduate groups at the University of California, Berkeley, and a member of Cancer Center at UCSF. She has received numerous recognitions and awards for her scientific achievements including her elections as a Fellow of the American Academy for the Advancement of Science, a member of the Institute of Medicine of the National Academy of Sciences, and a member of the American Academy of Arts and Sciences. She has been honored both by the Department of Defense (first Innovator Award) and the Department of Energy (the Lawrence Award and the first Distinguished Fellow in Biosciences) and received honorary doctorates from Pierre and Marie Curie University in Paris and University of Copenhagen. In 1997, Dr. Bissell served as President of the American Society for Cell Biology. A member of the American Association for Cancer Research since 1988, Dr. Bissell served on its Board of Directors from 1999-2001, and received the AACR-G.H.A. Clowes Memorial Award in 1999.

For biographical information on Bissell, high-resolution photographs and the complete award citation, contact Greg Lester at lester@aacr.org/267-646-0554.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

The Pezcoller Foundation was established in 1982 by Professor Alessio Pezcoller, a dedicated Italian surgeon who made important contributions to medicine during his career and who, through his foresight, vision, and generosity leading to the formation of the Foundation, has stimulated others to make significant advances in cancer research. The AACR and the Pezcoller Foundation established this award in 1997 to recognize a major scientific discovery in basic or translational research. It honors a scientist who has made a major discovery in basic cancer research or who has made significant contributions to translational research, who continues to be active in research and has a record of recent, noteworthy publications, and whose ongoing work holds promise for continued, substantive contributions to progress in the field of cancer.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

America’s Oldest and Largest Cancer Research Organization Elects Leadership

registration@aacr.org () — Mon, 26 Mar 2007 12:00:00 GMT

American Association for Cancer Research chooses officers, directors and nominating committee members for 2007 and beyond

PHILADELPHIA- Raymond N. DuBois, M.D., Ph.D. of Vanderbilt University has been elected president-elect of the American Association for Cancer Research. He succeeds William N. Hait, M.D., Ph.D., Senior Vice President and Worldwide Head for Hematology Oncology Research Development Johnson & Johnson, who will become president. Geoffrey M. Wahl, Ph.D. of The Salk Institute for Biological Sciences in La Jolla, Calif., who has served as AACR president for the 2006-2007 term, will fulfill the role of past president.

These positions are effective April 16, 2007, at the AACR Annual Meeting 2007 in Los Angeles, Calif. The president, president-elect and past president serve terms of one year, comprising the period between annual meetings.

Raymond N. DuBois, M.D., Ph.D., stepped down early last month as director of the Vanderbilt-Ingram Cancer Center. This summer, Dr. DuBois will join The University of Texas M. D. Anderson Cancer Center as provost and executive vice president.

His research focuses on determining the role of certain inflammatory mediators in progression of colorectal cancer. One of the goals of this research is to develop better strategies for prevention and early detection. He and his lab found that COX-2 is elevated in pre-malignant polyps and its presence directly influences progression of and risk for colorectal cancer. DuBois's team is now focused on developing safer alternatives that target the cyclooxygenase pathway further downstream. They recently co-discovered a new tumor suppressor gene, 15-prostaglandin dehydrogenase (15-PGDH), which is lost in almost all advanced colorectal cancers. Currently his group is determining how 15-PGDH is regulated, and how its expression may be re-established. They are also evaluating key receptor signaling pathways affected by prostaglandins that may serve as useful targets for cancer prevention and/or treatment.

"The AACR is at a critical stage in its evolution as it prepares to celebrate 100 years of progress in the fight against cancer," said Dr. DuBois. "By supporting cancer research from the basic science laboratory all the way to late phase clinical trials, the AACR has taken on the crucial mission of supporting work that will ultimately decrease morbidity and mortality from cancer."

Dr. DuBois is principal investigator on three research grants from the National Institutes of Health, including one MERIT award from the National Institute of Diabetes and Digestive and Kidney Disease. His research also is supported by funding from the National Colorectal Cancer Research Alliance established by CBS Evening News anchor Katie Couric.

Dr. DuBois is on the editorial boards for the AACR journal Clinical Cancer Research, and CR, the AACR's magazine about people and progress in cancer. He is the associate editor of Cancer Research, and is a member of the publications committee, as well as many other AACR committees. Additionally, he has served as chair or co-chair for several AACR Special Conferences on the topic of colorectal cancer.

Dr. DuBois, a Texas native, received his M.D. at The University of Texas Health Science Center in San Antonio and his Ph.D. at University of Texas Southwestern Medical School in Dallas.

William N. Hait, M.D., Ph.D., recently began a new position as Senior Vice President and Worldwide Head for Hematology Oncology Research Development at Johnson & Johnson. Previously he was the director of The Cancer Institute of New Jersey and professor of medicine and pharmacology and associate dean for oncology programs at the University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School.

Dr. Hait's laboratory work focuses on two major research interests: determinants of sensitivity to anticancer treatments and signal transduction systems uniquely altered in malignant cells. He is currently the editor-in-chief of Clinical Cancer Research and co-editor of Holland and Frei's Cancer Medicine. He has also served as chair or co-chair of several AACR meetings, think tanks, and committees relevant to clinical translational research. He is a member of the Board of Scientific Advisors of the National Cancer Institute and serves on several cancer center advisory boards.

Geoffrey M. Wahl, Ph.D., is a professor in the Gene Expression Laboratory of The Salk Institute for Biological Studies in La Jolla, Calif., and an adjunct professor in the Department of Biology of the University of California, San Diego.

Dr. Wahl's laboratory is currently studying the molecular mechanisms that regulate the p53 stress response pathway, implementing drug and drug combinations to activate this pathway in cancer cells, and identifying and analyzing tissue-specific stem cells and cancer stem cells. Dr. Wahl has served the AACR as a member of the Board of Directors; program chairperson of the 95th Annual Meeting; member of the editorial boards of Molecular and Cellular Biology, DNA Repair, Molecular Cancer Research and Cell Growth and Differentiation; as well as holding numerous other special conference chairs and committee posts.

Five new members were elected to the AACR Board of Directors for the 2007-2010 term. They are:

Judy E. Garber, M.D., M.P.H., director of the Cancer Risk and Prevention Clinic/Clinical Genetics Program; associate professor of Medicine, clinical associate in Medicine, and attending physician, Medical Oncology Service, Dana-Farber Cancer Institute; associate physician in Medicine and attending physician, Medical Service, Brigham and Women's Hospital, Boston, Mass.

Joe W. Gray, Ph.D., director of the Division of Life Sciences, and associate director of Life and Environmental Sciences, Lawrence Berkeley National Laboratory; adjunct professor in the Department of Laboratory Medicine, University of California San Francisco School of Medicine; program leader of Breast Oncology and Cancer Genetics; University of California San Francisco Comprehensive Cancer Center, San Francisco, Calif.

Daniel A. Haber, M.D., Ph.D., director of the Massachusetts General Hospital Cancer Center; director, Center for Cancer Risk Analysis, and physician, Massachusetts General Hospital; Laurel Schwartz Professor of Oncology and professor of Medicine, Harvard Medical School; chair, Program in Cancer Genetics, Dana Farber-Harvard Comprehensive Cancer Center, Boston, Mass.

V. Craig Jordan, OBE, Ph.D., D.Sc., Alfred G. Knudson Chair in Cancer Research and vice president and research director for Medical Sciences, Fox Chase Cancer Center; adjunct professor, Cancer Biology, Abramson Family Cancer Center, University of Pennsylvania, Philadelphia, Pa.

Eileen P. White, Ph.D., associate director for Basic Science, member and program leader, Cancer Institute of New Jersey, New Brunswick, N.J.; professor, Department of Molecular Biology and Biochemistry, Rutgers University; resident faculty member, Center for Advanced Biotechnology and Medicine; adjunct professor, Department of Surgery, University of Medicine and Dentistry of New Jersey, Piscataway, N.J.

Four new members were elected to the AACR Nominating Committee for the 2007-2009 term. They will serve alongside the four current members to develop the candidate slates for president-elect and director. With the board of directors, they will also choose the candidates for the next nominating committee slate. Newly-elected members are:

Stephen H. Friend, M.D., Ph.D., executive vice president, Advanced Technologies and Oncology, Merck Research Laboratories, Merck & Co., Inc., West Point, Pa.; president, Aton Pharma, Inc., Tarrytown, N.Y.; president, Rosetta Inpharmatics, LLC, Seattle, Wash.

Elaine V. Fuchs, Ph.D., Rebecca C. Lancefield Professor, professor of Laboratory of Mammalian Cell Biology and Development, and Howard Hughes Medical Institute Investigator, Rockefeller University, New York, N.Y.

Jeffrey M. Trent, Ph.D., president and scientific director, Translational Genomics Research Institute, Phoenix, Ariz; adjunct professor of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Md.

Zena Werb, Ph.D., professor of Anatomy and vice chair of the Department of Anatomy, University of California, San Francisco; faculty biologist, Lawrence Berkeley National Laboratory, Berkeley, Calif.

For further information on any of the newly elected officers, board of directors, or nominating committee members please e-mail decicco@aacr.org.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Angela DeCicco
(215) 440-9300 ext. 104
decicco@aacr.org

AACR’s Sixth Annual Landon Awards Recognize Richard Kolodner for Fundamental Research on DNA Mismatch Repair and Douglas Lowy and John Schiller for Landmark HPV Vaccine Work

registration@aacr.org () — Thu, 22 Mar 2007 12:00:00 GMT

PHILADELPHIA - Scientists whose discoveries have led to fundamental advances in the science and treatment of cancer are the recipients of two prestigious international prizes offered by the Kirk A. and Dorothy P. Landon Foundation and the American Association for Cancer Research.

The Kirk A. Landon-AACR Prize for Basic Cancer Research and Dorothy P. Landon-AACR Prize for Translational Cancer Research are the largest such awards offered to cancer researchers from a professional society of their peers. The recipients for each prize receive an unrestricted cash award of $200,000 and present a scientific lecture at the AACR Annual Meeting, held this year from April 14-18 in Los Angeles, California.

This year's winner of the Kirk A. Landon-AACR Prize for Basic Cancer Research is Richard D. Kolodner, Ph.D., member of the Ludwig Institute for Cancer Research, and professor of medicine and member of the Moores Cancer Center at the University of California, San Diego School of Medicine. Kolodner is recognized for his fundamental discoveries in the field of DNA mismatch repair and its connection to human cancer.

"DNA mismatch repair has proven to be a fundamental concept in cancer genetics and we are proud to honor Richard Kolodner for his work," said Margaret Foti, Ph.D., M.D. (h.c.), AACR's chief executive officer. "The ingenuity and resourcefulness that led to Dr. Kolodner's discoveries strongly represents the spirit with which the Kirk A. Landon-AACR Prize for Cancer Research is given."

This year's Dorothy P. Landon-AACR Prize for Translational Cancer Research is awarded to National Cancer Institute researchers Douglas R. Lowy, M.D., and John T. Schiller, Ph.D., for research leading to the development of the human papillomavirus vaccine. Lowy is chief of NCI's Laboratory of Cellular Oncology and head of NCI's Signaling and Oncogenesis Section. Schiller is senior investigator in NCI's Laboratory of Cellular Oncology and head of NCI's Neoplastic Disease Section.

"It is our great privilege to honor Douglas Lowy and John Schiller, whose work on the HPV vaccine not only highlights their research excellence but also their deep respect for humanity," Foti said. "Their achievements will save a great many lives and provide a clear example of the continuing importance for translational cancer research."

The Kirk A. Landon-AACR Prize for Basic Cancer Research

Kolodner's major contribution to cancer biology has been in defining the molecular mechanisms of DNA mismatch repair, the ability of cells to repair genetic errors that could disrupt the stability of DNA. His work has demonstrated how inherited defects in mismatch repair are directly linked to human cancer. Kolodner was the first to tackle the study of mismatch repair through a creative combination of bacteria/yeast genetics and biochemistry, along with human genomic approaches. He is a pioneer in using the power of yeast genetics to uncover multiple genes and the interactions between them that keep the genome stable, and he has continued to make fundamental contributions to this field through the combination of genetics and biochemistry.

"Richard Kolodner has played a seminal role in our understanding of cancer genetics and pioneered many of the techniques that have become standard tools in cancer research," said Inder M. Verma, Ph.D., professor of biology at University of California, San Diego, faculty at the Salk Institute for Biological Sciences, and chair of the committee that selected Kolodner for the Landon Award.

"Kolodner's research has provided the research community with the tools and knowledge it needs to progress in the fight against cancer," Verma said. "His discovery of the role of faulty mismatch repair in hereditary nonpolyposis colorectal cancer, for example, has directly led to the use of genetic screening for the disease."

Kolodner has served on numerous advisory and review boards including the National Cancer Institute Board of Scientific Councilors and presently serves on the Howard Hughes Medical Institute Scientific Review Board. Dr. Kolodner has received numerous honors and awards, including most recently: a National Institutes of Health MERIT Award; the Charles S. Mott Prize from the General Motors Cancer Research Foundation; the Mutation Research Award for Scientific Excellence; the Ernst W. Bernter Award from the M.D. Anderson Cancer Center; election to the National Academy of Sciences (USA); and the Katharine Berkan Judd Award from the Memorial Sloan-Kettering Cancer Center.

The Dorothy P. Landon-AACR Prize for Translational Cancer Research

Douglas R. Lowy and John T. Schiller played an integral role in the development of the human papillomavirus vaccine against cervical cancer, performing fundamental research regarding the nature of the virus, animal studies, and a Phase I trial in humans. It was their demonstration that subunits of the outer shell of the HPV, the capsid proteins, were capable of inducing antibodies, which meant the capsid proteins could be used as both a serological test and a vaccine against HPV infection.

Their ongoing research directly led to the first HPV vaccine, approved by the FDA in 2006, which has the potential to drastically reduce the incidence of cervical cancer in women.
"Lowy and Schiller paved the way for the HPV vaccine, one of the most remarkable public health achievements in cancer research history," said William N. Hait, M.D., Ph.D, professor of medicine at the University of Medicine and Dentistry of New Jersey, president-elect of AACR, current director of the Cancer Institute of New Jersey, future senior vice president and head, Worldwide Oncology R&D at Johnson & Johnson, and chair of the committee that selected Schiller and Lowy for the Landon Award.

"It is hard to imagine a clearer example of how laboratory research can make a difference in our everyday lives," Dr. Hait said. "In addition to their fine research, their continuing engagement in the public health debate surrounding the vaccine's application exemplifies them as science advocates of the truest kind."

Dr. Lowy has received the Wallace Rowe Award for Virus Research and has been a member of many scientific advisory boards, grants committees, and editorial boards. Schiller has received the Society for Investigative Dermatology's Naomi Kanof Clinical Investigator Award and has served as an advisor to the World Health Organization and Gates Foundation on HPV vaccine-related matters.

The Landon/AACR Prizes in Cancer Research were launched in the summer of 2002 to promote and reward seminal contributions to our understanding of cancer through basic and translational cancer research. These distinguished scientific prizes are designed to bring heightened public attention to landmark achievements in the continuing effort to prevent and cure cancer through quality research.

For complete award citations and biographies and photos of award winners, contact Greg Lester at the AACR Department of Communications and Public Relations: 267-646-0554; lester@aacr.org

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

The Kirk A. and Dorothy P. Landon Foundation was created through a bequest from Mrs. Landon who willed that her estate be committed to medical research, especially cancer research and research into cancer-related diseases. R. Kirk Landon, son of Kirk A. Landon, serves as chairman of the Foundation's Board of Trustees. The Foundation accomplishes its mission through a variety of programs and initiatives, the first of which were the Landon-AACR Prizes.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

NIH Director Breaks With Bush Policy, Wants Limits Eased on Stem Cell Research

registration@aacr.org () — Tue, 20 Mar 2007 12:00:00 GMT

The director of the National Institutes of Health told a Senate panel March 19 that American scientists would be better served if they had access to more embryonic stem cell lines and federal funding restrictions imposed in 2001 were lifted.

The comments were Elias A. Zerhouni's boldest statement to date in favor of changing a policy implemented by President Bush. The president already has vetoed legislative attempts to change the policy, and has promised to veto them again if a House-passed bill (H.R. 3) is approved by the Senate, as is expected.

While Zerhouni--whom President Bush appointed in 2002--has said publicly that scientists need access to more stem cell lines, it is his first congressional testimony openly supporting a policy change. At a House appropriations hearing March 6, Zerhouni said that "I am convinced we need to really allow our scientists to do more of what we need to do." However, he did not specifically comment on the president's policy during that hearing.

Zerhouni made his latest comments in a response during a budget hearing to a question from Sen. Tom Harkin (D-Iowa), chairman of the Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies.

'The Answer Is Yes.'

Harkin asked whether scientists would have a better chance of finding cures "if current restrictions were lifted," so that they could use federal dollars on research using embryonic stem cell lines created after Aug. 9, 2001. "It's clear today that American scientists would be better served if we allowed our scientists to have access to more cell lines," Zerhouni said. "So the answer is yes."

Harkin and subcommittee ranking member Sen. Arlen Specter (R-Pa.) are also the primary supporters of S. 5, a bill identical to H. 3 that would allow excess embryos from in vitro fertilization clinics to be used for medical research. The Senate is expected to vote on the bill in April.

The agency "has done a great job" in overseeing the stem cell research since 2001, the NIH director said. However, since 2004 those lines have exhibited instability and have proven to be contaminated with mouse feeder cells, he said.

"Since 2004, it's very clear from the point of view of science that these cell lines will not be sufficient to do all the research we need to do," he said.

Harkin called Zerhouni's comments "courageous."

Stem cell research is really about understanding how DNA is programmed and reprogrammed, Zerhouni said, and therefore scientists should be allowed to pursue all angles of stem cell research, because embryonic stem cells represent unprogrammed DNA, whereas adult stem cells are programmed.

"It's basically the software of life that we're talking about," he said.

Patchwork of Regulations

Further, Zerhouni said that NIH--the world's largest biomedical organization--needs to oversee this area of research, and not let it be regulated by a patchwork of state and local laws. The agency has the depth and oversight system to oversee the research, he said, and it was time for national policy makers to find common ground, so NIH can continue to maintain its role as the nation's leader of biomedical research.

"This is not a one-mile race; this may be a marathon," he said.

Zerhouni referred to the Recombinant DNA Advisory Committee that NIH formed in the late 1970s, giving NIH the lead in a new field of research that eventually led to the biotechnology industry.

"This is the kind of role NIH can play," he said. "It's important for us not to function with one hand tied behind our backs."

Flat Funding

Zerhouni was testifying at a Senate hearing on the NIH budget, which President Bush proposed at $28.9 billion for fiscal year 2008, a slight increase over the president's proposal for 2007. However, the White House's fiscal 2008 proposed appropriation is the same as the actual amount NIH will receive in fiscal 2007, because of a joint funding resolution that added $620 million to the agency's budget.

Harkin said that, with inflation, NIH funding has dropped by about 13 percent in real terms since the budget was doubled in 2003.

"That cut threatens to squander our nation's investment in biomedical research, delay new cures and treatments, and discourage the next generation of young investigators from entering the field," the Iowa senator said.

Specter said he and Harkin plan to go to the Senate floor and request more money for NIH. While not giving a dollar amount, Specter said they will request "the most we think we can get that's realistic."

"Health is our most important capital asset. Without health care, there's nothing any of us could do," Specter said. "The best way to reduce health care costs is to eliminate the majority of maladies to prevent illness. We are blind to this very, very important objective."

Scientists' Report

A report by a group of university scientists released directly after the Senate hearing said that stagnant funding of the NIH could lead NIH to lose its place as the world's leader in biomedical research. According to the report, 80 percent of grant applications are unfunded, and certain NIH components, such as the National Cancer Institute, report that they can fund just 11 percent of research project grant applications.

The group maintained that perennially flat funding of NIH has halted promising research in mid-stream, challenged seasoned researchers to continue to achieve scientific progress, and threatened the future of young investigators pursuing careers in academic research. If left unaddressed, these problems could undermine U.S. global leadership in biomedical research, the report warns.

The report, "Within Our Grasp--Or Slipping Away? Assuring a New Era of Scientific and Medical Progress," argues that research momentum gains have slowed, and in some cases may be lost, if flat funding continues

"The number of drugs moving into the pipeline that are based on our new, more profound genetic and molecular understanding of cancer is extraordinary--and there's no money to handle the testing of these compounds," Joan Brugge, chair of the Department of Cell Biology at Harvard Medical School and co-author of the report, said in a press statement.

Zerhouni's prepared testimony is available at http://www.nih.gov/about/director/budgetrequest/fy2008directorssenatebudgetrequest.htm . The report, "Within Our Grasp--Or Slipping Away? Assuring a New Era of Scientific and Medical Progress," is available at http://hms.harvard.edu/public/news/nih_funding.pdf.

Researchers Use Poliovirus to Destroy Neuroblastoma Tumors in Mice

registration@aacr.org () — Thu, 15 Mar 2007 12:00:00 GMT

PHILADELPHIA-- The cause of one notorious childhood disease, poliovirus, could be used to treat the ongoing threat of another childhood disease, neuroblastoma. In the March 15 issue of Cancer Research, researchers from Stony Brook University report that an attenuated -- or non-virulent -- form of poliovirus is effective in obliterating neuroblastoma tumors in mice, even when the mice had been previously vaccinated against the virus.

By its nature, poliovirus destroys the cells it infects in an attempt to replicate copies of itself. When released from the cells it kills, the replicated particles then attack surrounding cells. The Stony Brook researchers took advantage of this viral property by injecting a stable, attenuated strain of poliovirus directly into neuroblastoma tumors transplanted into 12 mice engineered to contract polio. The virus was able to destroy tumors in all 12 mice; however tumors reoccurred in two mice by the end of the 180-day study period.

None of the mice experienced any ill effects from the virus itself. According to the researchers, any viral particles that make it to the bloodstream would be destroyed by antibodies created through poliovirus vaccination. The researchers believe that their findings, if developed to work in humans, could represent a safe, practical means of treating a deadly childhood cancer and possibly many other cancers in adults.

"A tamed poliovirus represents a significant step in finding viral treatments that can kill tumors without harming patients," said Hidemi Toyoda, M.D., Ph.D., a pediatrician and postdoctoral research fellow in Stony Brook's Department of Molecular Genetics and Microbiology. "Effectively, we have harnessed a virus that was deadly in children just a few decades ago, namely polio, and used an essential aspect of its nature to destroy a disease that is deadly today."

Surprisingly, the researchers also discovered that the poliovirus treatment effectively protected the mice against new tumor growth, a significant factor when fighting a disease like neuroblastoma, which is known to reoccur following chemotherapy.

Neuroblastoma is the most common form of solid tumor in children. It is a cancer of the sympathetic nervous system, the network of nerves that regulate unconscious body activities such as breathing. The cancer most often occurs as a mass or lump on the adrenal glands, which are located on top of the kidneys.

While chemotherapy and radiation therapy are generally effective for some cases of the disease, the prognosis is poor for children with high-risk neuroblastoma.

"Neuroblastoma can be very difficult to treat and the chemotherapies used can lead to health problems later in life," Toyoda said. "In combination with conventional therapy, a poliovirus treatment could reduce the exposure of a child to chemotherapy or radiation and lower the risk of harmful side effects."

To test the effectiveness of poliovirus against cancer tissue, the researchers first had to develop a safe form of the virus. Toyoda and his colleagues work in the laboratory of Stony Brook professor Eckard Wimmer, Ph.D., who in 2002 synthesized poliovirus from its basic chemical components. Based on the properties of the synthetic poliovirus, Wimmer created the highly attenuated virus used in this study by substituting a single nucleotide, located in a functionally important portion of the viral RNA genome called a "spacer region", with an essential regulatory gene removed from elsewhere in the viral genome.

According to Jeronimo Cello, Ph.D., senior author of the Cancer Research paper and research assistant professor at Stony Brook, this engineering feat is like putting a double failsafe into the virus.

"The engineered poliovirus cannot produce neurovirulent copies of itself if the spacer region remains interrupted," said Cello. "And in the unlikely event that the regulatory gene element is deleted, the virus would not be able to reproduce."

To test the virus' ability to destroy neuroblastoma the researchers constructed a transgenic mouse model that allows growth of neuroblastoma cells and carries the human gene for CD155, which codes for the receptor that allows poliovirus to enter cells. The mice were then vaccinated against poliovirus.

Since most humans are immunized against poliovirus, Toyoda and his colleagues needed to know whether such immunization would interfere with the use of the virus in tumor therapy. By injecting the virus directly into the mouse tumors, the researchers demonstrated that it was possible to reach their target and still avoid interacting with the anti-poliovirus antibodies generated by the vaccine.

Not only did the poliovirus prove effective in destroying the tumors, the treatment with virus also seemed to prevent tumors from recurring. Subsequent transplanted tumors were also destroyed, presumably through an enhancement of anti-tumor immune response, say researchers. Since the poliovirus was gone from the system, however, the researchers are unsure of exactly how that immune response occurred.

"This immunity against neuroblastoma acquired by the animals is still something of a mystery, one that we hope to address in future studies," Toyoda said. "But it is an encouraging sign since neuroblastoma are known to relapse quite frequently."

The study was funded by the National Institute of Allergy and Infectious Diseases and the Stony Brook Sunrise Fund for Pediatric Cancer.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

Large-Scale Japanese Study Finds Soy Protective against Localized Prostate Cancer, But Not Advanced Prostate Cancer

registration@aacr.org () — Thu, 15 Mar 2007 12:00:00 GMT

PHILADELPHIA - The largest study examining the relationship between the traditional soy-rich Japanese diet and development of prostate cancer in Japanese men has come to a seemingly contradictory conclusion: intake of isoflavone chemicals, derived largely from soy foods, decreased the risk of localized prostate cancer but increased the risk of advanced prostate cancer.

The prospective study of 43,509 men, published in the March issue of Cancer Epidemiology, Biomarkers & Prevention, suggests that the effects of isoflavones on prostate cancer development may differ according to disease stage, say researchers at the National Cancer Center in Japan.

One possible explanation is that isoflavones may delay the progression of latent prostate cancer only; once tumors lose estrogen-receptor beta expression and become aggressive, isoflavones may fail to protect against the development of advanced cancer, and might even increase the risk of progression, possibly by reducing serum testosterone, researchers say. It is also possible that advanced and localized prostate cancer may be different tumor subtypes, which may react differently to isoflavones.

"The present findings provide no clear understanding of when or how localized cancer will develop to aggressive cancer, and of the related effect of isoflavones," said the study's first author, Norie Kurahashi, M.D., of the Epidemiology and Prevention Division of the National Cancer Center.

"Given that Japanese consume isoflavones regularly throughout life, we do not know the period during which the effects of isoflavones on prostate cancer are preventive, and further research is required to find that out, including well-designed clinical trials," she said.

Until those studies are done, the researchers recommend that Japanese men continue to consume isoflavones through their food and not through supplements.

"Consumption of isoflavones from traditional Japanese food throughout life may protect against the incidence of prostate cancer, but we cannot recommend the use of isoflavones from supplements for people who do not regularly consume these chemicals, because the relationship between isoflavones and the risk of advanced prostate cancer is not yet clear," Kurahashi said.

Isoflavones act as both strong antioxidants and plant-based estrogens. Soybeans are the most common source of isoflavones, especially genistein and daidzein, which have been shown in some animal studies to exert a protective effect against prostate cancer.

Japanese men eat significantly more soy-based foods than do Western men, and the incidence of prostate cancer is much lower in Asian countries than in Western countries. Still, reviews of latent, or clinically insignificant, prostate cancer findings in autopsy reports have revealed no difference between the populations so scientists have theorized that isoflavones stop latent cancers from developing further.

But because smaller epidemiological studies in Japan have reached differing conclusions about the protective effects of soy on prostate cancer development, this research team conducted the most comprehensive analysis to date. They polled thousands of men age 40-69 about their consumption of 147 foods, the most popular of which were miso soup (primarily made from fermented soybeans), natto (also a product of fermented soybeans) and tofu, made from soy milk. Japanese consume miso soup more frequently, usually daily, than other soy foods, and miso, natto, and tofu account for about 90 percent of the population's consumption of daidzein and genistein, according to Kurahashi.

The researchers then followed participants from 1995 through 2004 and found that 307 men were diagnosed with prostate cancer. In this group, 74 cases were advanced, 218 were confined to the prostate organ, and 15 were of undetermined stage.

They concluded that intake of genistein, daidzein, miso soup and soy food had no overall link to diagnosis of prostate cancer. However, they calculated that the risk of developing localized prostate cancer was 50 percent lower in men who ate the most isoflavones compared to men who ate the least - meaning that men in the top category ate between two and three times as much isoflavone-rich food.

However, in a discovery they cannot explain, they also calculated that the risk of developing advanced prostate cancer was twice as high in men who consumed two or more bowls of miso soup a day than in men who ate less than one bowl of soup.

They also found that the protective effect of isoflavone-rich food was strongest in men who were older than 60: the more isoflavones they ate, the more they reduced their risk of developing localized prostate cancer. "Isoflavone may be protective for localized prostate cancer only in men aged more than 60 years, and may not have a protective effect in the early stage of prostate cancer in younger men," the researchers conclude in their study.

The inconsistencies in the finding - that isoflavones decreased the risk of localized prostate cancer, but not the risk of advanced prostate cancer - could be errors in food measurement, or could be due to the fact that the number of participants who developed advanced prostate cancer was small, said Kurahashi. Or, as researchers speculate, isoflavones could interact with the estrogen receptor on prostate tissue enough to inhibit production of testosterone, which can fuel prostate cancer. When tumors lose all of their estrogen receptors and stop responding to isoflavone-induced hormonal interference, they grow aggressively.

"A broad body of research is required to clarify the timing and period of isoflavones' preventive effect on prostate cancer development," Kurahashi said.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Researchers Wake Up Viruses Inside Tumors to Image and Then Destroy Cancers

registration@aacr.org () — Thu, 01 Mar 2007 12:00:00 GMT

PHILADELPHIA -- Researchers have found a way to activate Epstein-Barr viruses inside tumors as a way to identify patients whose infection can then be manipulated to destroy their tumors. They say this strategy could offer a novel way of treating many cancers associated with Epstein-Barr, including at least four different types of lymphoma and nasopharyngeal and gastric cancers.

In the March 1 issue of Clinical Cancer Research, a team of radiologists and oncologists from Johns Hopkins Medical Institutions describe how they used two agents already on the market - one of which is the multiple myeloma drug Velcade - to light up tumor viruses on a gamma camera. The technique is the first in the new field of in vivo molecular-genetic imaging that doesn't require transfecting tumors with a "reporter" gene, the scientists say.

"The beauty of this is that you don't have to introduce any reporter genes into the tumor because they are already there," says radiologist Martin G. Pomper, M.D., Ph.D. "This is the only example we know of where it is possible to image activated endogenous gene expression without having to transfect cells."

A variety of blood and solid cancers are more likely to occur in people who have been infected with the Epstein-Barr virus (EBV), but not everyone with these cancers has such infections. For those who do, researchers, such as Hopkins oncologist and co-author Richard F. Ambinder, M.D., Ph.D., have been working on ways to activate the reproductive, or "lytic" cycle, within the virus to make it replicate within the tumor cell. When enough viral particles are produced, the tumor will burst, releasing the virus. In animal experiments, this experimental therapy, called lytic induction therapy, results in tumor death.

As the first step in this study, researchers screened a wide variety of drugs to see if any of them could reawaken the virus. They were fortunate in that one of the genes that is expressed upon viral lytic induction is EBV's thymidine kinase (EBV-TK), an enzyme that helps the virus begin to reproduce. This kinase is of interest because researchers know its "sister" kinase, the one produced by the herpes simplex virus, can be imaged by an injected radiolabeled chemical (FIAU), which can then be imaged using a gamma camera.

"To perform molecular-genetic imaging, we have always had to infect cells with active herpes simplex virus so that they can replicate, express TK, and only then could we use the FIAU tracer to make the cells light up," Pomper says. "So we were hoping to find a way to turn latent Epstein-Barr virus on in these cancers, and use the thymidine kinase it then produces to enable us to see the virus-associated tumors with radiolabeled FIAU."

The researchers screened 2,700 agents until they hit upon Velcade, a targeted chemotherapy drug already approved for use in multiple myeloma. "We were both surprised and lucky," he says. "Velcade is a proteasome inhibitor, but it also induces the lytic cycle thereby activating the TK in the Epstein-Barr virus. Once the TK is activated, we can image the tumors."

To test their findings, the researchers used mice carrying human Burkitt's lymphoma, a cancer often associated with Epstein-Barr viral infection. Tumors glowed in mice given Velcade followed by an injection of FIAU, but not in mice that weren't given Velcade. Mice whose Burkitt's lymphoma did not contain Epstein-Barr virus also did not respond to either Velcade or FIAU, according to researchers.

"Velcade woke up the virus in the tumors, which increased viral load by 12-fold, all the while cranking out TK," Pomper says. "An injection of FIAU made it easy to image the tumors with virus in them."

The method is highly sensitive, he says: as few as five percent of the cells within the tumor mass needed to be induced into the lytic cycle in order to be detected.

Not only can FIAU light up the tumors, it can also potentially kill them, Pomper says. For imaging purposes, FIAU can carry a radionuclide that emits a low energy gamma photon, but it can also be engineered to carry therapeutic radionuclides, which are lethal to cells in which TK is activated.

Results of this study suggests that this strategy could be applied to other viruses associated with tumors, and that other drugs may potentially be used to activate these viruses, Pomper says. "Velcade is only one of an array of new, as well as older agents, that can induce lytic infection, and a particular agent could be tailored for use in a specific patient through imaging," he says.

The study was funded by the National Cancer Institute.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0667
lester@aacr.org

Green Tea and COX-2 Inhibitors Combine to Slow Growth of Prostate Cancer

registration@aacr.org () — Thu, 01 Mar 2007 12:00:00 GMT

PHILADELPHIA -- Drinking a nice warm cup of green tea has long been touted for its healthful benefits, both real and anecdotal. But now researchers have found that a component of green tea, combined with low doses of a COX-2 inhibitor, could slow the spread of human prostate cancer.

In the March 1 issue of Clinical Cancer Research, researchers from University of Wisconsin-Madison demonstrate that low doses of the COX-2 inhibitor celecoxib, administered with a green tea polyphenol called pigallocatechin-3-gallate (EGCG), can slow the growth of human prostate cancer. Their experiments were performed in cell cultures and in a mouse model for the disease.

"Celecoxib and green tea have a synergistic effect -- each triggering cellular pathways that, combined, are more powerful than either agent alone," said Hasan Mukhtar, Ph.D., professor of dermatology at the University of Wisconsin and member of Wisconsin's Paul Carbone Comprehensive Cancer Center. "We hope that a clinical trial could lead to a preventative treatment as simple as tea time."

Previous research has linked the cyclooxygenase-2 enzyme, commonly known as COX-2, to many cancer types, including prostate cancer, said Mukhtar. Mukhtar and his colleagues have previously shown COX-2 inhibitors like celecoxib (known under the brand name Celebrex^TM) suppress prostate cancer in animal models. COX-2 inhibitors also have been shown to cause adverse cardiovascular effects when administered at high doses over long durations.

In 2004, Mukhtar and his colleagues demonstrated that green tea polyphenol EGCG has cancer-fighting abilities of its own. Their study, published in Cancer Research, showed that EGCG can modulate the insulin-like growth factor-1 (IGF-1)-driven molecular pathway in a mouse model for human prostate cancer, pushing the cells toward programmed cell death (apoptosis).

"We believed that COX-2 inhibitors may still prove beneficial if used in combination with complementary agents," Mukhtar said. "Our studies showed that the additive effect of green tea enables us to utilize the cancer-fighting abilities of COX-2 inhibitors, but at lower, safer doses."

In this latest research, Mukhtar and his colleagues looked at the effects of the two substances on cultured human prostate cancer cells. Alone, both EGCG and NS-398, a COX-2 inhibitor similar to celecoxib, demonstrated the ability to slow cancer cell growth and limit the presence of known cancer-promoting proteins within the cell samples. Together, EGCG and NS-398 suppressed cell growth by an additional 15 to 28 percent.

The researchers repeated the experiment in mouse models of prostate cancer, using celecoxib and an oral suspension of the decaffeinated green tea polyphenol. By using pharmacy-grade celecoxib and actual tea, they had hoped to replicate real-life conditions. "The idea is that it would be easier to get people to drink green tea than it would be to take an additional dietary supplement," Mukhtar said.

In mice that were not treated with either substance, the tumor volume averaged 1,300 cubic millimeters, whereas mice given either the tea or celecoxib had tumors averaging 835 cubic millimeters and 650 cubic millimeters, respectively. Tumors taken from mice given both agents, however, measured on average a volume of 350 cubic millimeters.

In parallel to tumor growth inhibition, mice that received a combination of green tea and celecoxib registered a greater decrease in prostate specific antigen (PSA) levels compared to that in celecoxib alone or green tea alone treated animals. PSA is a protein produced by the cells of the prostate and is used as a marker for detection and progression of prostate cancer. These results, combined with a marked decrease in the presence of cancer-promoting proteins, offered clear indications that green tea and celecoxib, combined, could be useful in slowing prostate cancer growth, Mukhtar said.

"Prostate cancer typically arises from more than one defect in the cellular mechanics, which means that a single therapeutic might not work fighting a particular cancer long-term," Mukhtar said. "If tests in human trials replicate these results, we could see a powerful combined therapy that is both simple to administer and relatively cost effective."

The study was funded by the National Cancer Institute.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Gene Profiling Predicts Resistance to Breast Cancer Drug Herceptin

registration@aacr.org () — Tue, 20 Feb 2007 12:00:00 GMT

PHILADELPHIA -- Using gene chips to profile tumors before treatment, researchers at Harvard and Yale Universities found markers that identified breast cancer subtypes resistant to Herceptin, the primary treatment for HER2-positive breast cancer. They say this advance could help further refine therapy for the 25 to 30 percent of breast cancer patients with this class of tumor.

In the February 15 issue of Clinical Cancer Research, the researchers found that HER2-positive tumors that did not respond to Herceptin expressed certain basal markers, growth factors and growth factor receptors. One of these, insulin-growth factor receptor 1(IGF-1R), was associated with a Herceptin response rate that was half that of tumors that did not express IGF-1R.

They also discovered that resistant tumors continue to over-express the HER2 growth factor protein -- an important finding given that many scientists had thought that loss of HER2 was likely responsible for Herceptin resistance.

"Herceptin has revolutionized the care of HER2-positive breast cancer for many patients, but unfortunately, not for some. This work demonstrates that digging deeper into the molecular subtypes of these tumors helps us understand why some tumors are resistant and may point to ways to remedy that," said the study's lead author, Lyndsay Harris, M.D., associate professor and Director of the Breast Cancer Disease Unit at Yale University Medical Center.

If additional studies validate these findings, it may be possible to select those patients that will be resistant to Herceptin and treat them with additional drugs to restore Herceptin sensitivity, according to Harris. "Our goal is to see what the tumor tells us before any treatment starts and tailor therapy accordingly," she said.

To determine Herceptin sensitivity, investigators took a small tumor biopsy from 48 patients with newly diagnosed and operable stage II/III breast cancer. They examined the biopsy tissue using both single and multi-gene microarrays, looking for RNA that has been activated to produce proteins.

They then treated the women with a combination of Herceptin and the chemotherapy drug Navelbine weekly for 12 weeks. Although this is not the first study to test Herceptin use before surgery, it is the first to examine the use of Navelbine, a drug approved for lung cancer treatment, in combination with Herceptin to treat HER2-positive tumors. "We were motivated to use Navelbine because we found it has few side effects when used to treat metastatic breast cancer," said Harris, who conducted much of the research study at Harvard before moving to Yale.

After treatment, the tumors were surgically removed and gene chips were again used to examine RNA transcription -- making these investigators the first to use such a technique on Herceptin treated tumors. "This kind of profiling has been done to look at response to chemotherapy drugs, but not at Herceptin resistance," Harris said.

The researchers then divided tumors into groups depending on how well they responded to therapy, and examined the baseline and post-therapy RNA profiles to find genes that were more commonly expressed in Herceptin sensitive and Herceptin resistant tumors.

They first found that some single gene markers, such as HER2 and ER (estrogen receptor), did not change in the majority of tumors. "That tells us that the cancer cells are still creating HER2 surface proteins even as Herceptin is being used, and that means HER2 loss does not appear to be a mechanism of resistance in early stage breast cancer," Harris said.

Then, using multigene chips, the researchers derived a bevy of transcribed genes that likely play a role in Herceptin resistance. Some, such as IGF-1R, were suspected, because this protein is frequently over-expressed in breast tumors, Harris says, but others were not. For example, non-responding tumors were more likely to express genes associated with basal-like breast cancer, which the researchers found to be surprising. "Most basal-like tumors are HER2-negative," Harris said.

Herceptin resistant tumors were also more likely to express a variety of growth factors, suggesting that "activation of parallel pathways may release tumors from dependence on HER2 proliferation and survival," she said.

Although the study was not designed to look at outcome, the researchers determined that 42 of 48 patients had a clinical response (16 complete responses and 26 partial responses) from the neoadjuvant treatment, and five patients experienced cardiotoxicity. After a median 2.6-year-follow-up, three of 48 patients relapsed and one died of her disease.

The study was funded by the National Cancer Institute's SPORE grant to the Dana-Farber/Harvard Cancer Center and the Department of Defense Clinical Translational Research Award granted to Dr. Harris in 2003.

For a PDF of this study, please e-mail decicco@aacr.org or ortiz@aacr.org

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

Shortening Chromosomes Cause for Earlier Cancer Onset in Families with Rare Syndrome

registration@aacr.org () — Thu, 15 Feb 2007 12:00:00 GMT

PHILADELPHIA -- In families with a high incidence of Li-Fraumeni syndrome, the ends of individuals' chromosomes act somewhat like a lit fuse, according to researchers at The Hospital for Sick Children in Toronto. Their findings detail how telomeres, the ends of the chromosomes, shorten with every successive generation, leading to more severe cancers at an earlier age.

Their results, published in the February 15 issue of the journal Cancer Research, could represent the first biological marker for clinical monitoring in families with Li-Fraumeni syndrome, and could shed light on the important area of aging in cancer research.

"We have known since 1990 that Li-Fraumeni was associated with inheritance of a mutated form of the p53 tumor suppressor gene, but we also noticed each generation developed cancer earlier than the preceding generation," said David Malkin, M.D., the study's principal investigator, and co-director of the Cancer Genetics Program at The Hospital for Sick Children at the University of Toronto. "By studying blood samples taken from families in which members have Li-Fraumeni, we have discovered that telomeres become shorter in each generation of disease carriers, leading to a genetic instability that primes them for progressively earlier cancers."

First discovered in 1969, Li-Fraumeni syndrome is an inherited disorder that causes a wide spectrum of cancers, including breast, brain, bone and soft tissue cancers. To develop the disorder, a child only needs to receive one mutated p53 gene from one parent. Typically, the disease causes cancers relatively early in life and can strike numerous times, in differing forms, throughout a patient's life. According to Malkin, the disease afflicts between one in 10,000 to 40,000 people, but the exact number cannot be accurately determined since the random nature of the cancers makes accurate diagnosis of Li-Fraumeni difficult.

A major mystery of the disease, according to Malkin, is how certain family members could develop cancer at different times, even though they all carried the identical p53 gene mutation. Malkin and his colleagues speculated that telomere attrition -- or the successive shortening of telomeres with each normal cell division -- could account for such genomic instability, a finding confirmed by their study of 45 members from nine families with Li-Fraumeni syndrome.

"We were able to look at the DNA of multiple members of families that carried Li-Fraumeni and, overwhelmingly, telomere length was shorter in children with cancer than in unaffected siblings or parents," Malkin said. "Children whose telomeres were shorter than their parents who had the disease typically began developing cancer at a much earlier age than their parents."

Telomeres are repeated sequences of DNA at the tips of every chromosome that function as a sort of genetic slack. As cells grow and divide throughout life, the chromosomes, which contain all of an individual's genetic information, replicate as well. The enzymes that create copies of chromosomes cannot, however, physically reach the very end of the chromosome, so they leave a minute bit of this telomere slack behind each time. This is known to researchers as the "end replication problem" and has made telomeres an important subject of research in the science of aging and cancer. While Malkin and his colleagues link telomeres to genetic instability and cancer in the context of Li-Fraumeni syndrome, other researchers have studied whether it might be possible to kill rapidly growing tumors by accelerating telomere attrition.

"The discovery of telomere attrition in Li-Fraumeni really highlights the role that telomeres may perform in other cancers as well," said Malkin. "For Li-Fraumeni families, this might provide a means of determining if a child should be screened for cancer."

According to Malkin, this discovery is only one step in the further understanding of how these inherited cancers develop. Further studies are needed to find the molecular mechanisms that link p53 mutations with telomere attrition.

Funding for this research was provided by the National Cancer Institute of Canada through the Canadian Cancer Society, and the SickKids Foundation.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

Active Lifestyle Reduces Risk of Invasive Breast Cancer

registration@aacr.org () — Thu, 15 Feb 2007 12:00:00 GMT

Researchers Say It's Never Too Late to Start Exercising

PHILADELPHIA -- Six or more hours per week of strenuous recreational activity may reduce the risks of invasive breast cancer by 23 percent, according to researchers from the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (UWCCC). Their report in the February issue of Cancer Epidemiology Biomarkers & Prevention, based on a survey of over 15,000 women, shows that exercise has a protective effect against invasive breast cancer throughout a woman's lifetime.

The results provide further evidence that for most women physical activity may reduce the risk of invasive breast cancer, the researchers concluded.

To gain further insights into the mechanisms of risk reduction for breast cancer, the researchers investigated the relationship between physical activity and breast cancer risk in a population-based case control study in Massachusetts, New Hampshire, and Wisconsin.

During structured telephone interviews, the researchers questioned 7,630 women without breast cancer, 1,689 survivors of in situ, or non-invasive, breast cancer and 6,391 survivors of invasive breast cancer, all between the ages of 20 and 69. They asked detailed questions about physical activity, occupation, family history of breast cancer, menopausal status, and body mass index.

According to the researchers, women who exercised had a reduced risk of developing invasive breast cancer provided they didn't have a family history of breast cancer. This reduction in risk was apparent whether the physical activity took place early in life, in the postmenopausal years, or in the recent past.

"A woman's hormone levels naturally fluctuate throughout her life, and we have found that exercise likely offers protection against breast cancer regardless of a woman's stage in life," said Brian Sprague, a UWCCC research assistant and lead author of the study. "The take-home message for women should be that it is never too late to begin exercising."

Previous research has linked high levels of estrogen to an increased risk for developing breast cancer. Women who exercise heavily are, in general, older at the time of the first period, and tend to have irregular periods and a shortened estrogen-producing phase, which translates in a lower body exposure to estrogen, the researchers say.

Similarly, postmenopausal women who are physically active have also been shown to have lower levels of estrogen. This reduction may explain why increased physical activity reduces the risk of breast cancer, according to Amy Trentham-Dietz assistant professor at the University of Wisconsin-Madison and member of the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center. Other potential mechanisms include prevention of weight gain, regulation of insulin sensitivity and alterations in immune function.

Taking all these factors into consideration, "intervention studies assessing the effect of physical activity on estrogen and other hormone exposure, and other biomarkers of risk would provide valuable insights on the mechanisms of physical activity in reducing breast cancer risk," said Trentham-Dietz.

"Further studies of population subgroups are necessary to gain a better understanding of the relation of physical activity to breast cancer risk, and to identify the groups most likely to gain benefit from it," said Trentham-Dietz. "Future research should also consider household activity in addition to recreational and occupational activities."

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

Survey Finds Perceived Risk of Recurrence Is Low in African American Breast Cancer Survivors

registration@aacr.org () — Thu, 15 Feb 2007 12:00:00 GMT

PHILADELPHIA - A unique survey of African American breast cancer survivors at heightened risk for hereditary breast cancer has found the majority do not believe they have an increased chance of developing the cancer again.

Researchers from the University of Pennsylvania, reporting in the February issue of Cancer Epidemiology, Biomarkers & Prevention, say these findings suggest it is important to ensure that African American women understand their risk of developing cancer and genetic counseling to address cultural beliefs and values may be one way of doing so.

"Having a personal and family history of breast cancer are known risk factors for breast cancer, and it is surprising and worrisome that most of these women with such a history don't recognize that risk," said the study's lead author, Chanita Hughes Halbert, Ph.D., assistant professor of psychiatry and Director of the Community and Minority Cancer Control Program at the University of Pennsylvania's Abramson Cancer Center.

Halbert's research focuses on understanding the socio-cultural underpinnings of cancer prevention and control behaviors among ethnically diverse populations so that interventions can be designed that reduce cancer morbidity and mortality.

One such intervention is genetic counseling that often includes testing whether a woman has a mutation in one of two genes (BRCA1/BRCA2); women with these genes are at greater risk for developing breast cancer than women without alterations in those genes.

In an earlier study, Halbert found that African American women with a family history of breast cancer had a lower risk perception than did Caucasian breast cancer survivors. In this study, she and a team of researchers at Penn attempted to tease apart the factors that might lead to this disparity, one of which, they believe, is the way survivors think about time.

"Attitudes about time are aspects of a cultural worldview," Halbert said. "We thought, based on earlier work, that African American women who were most concerned about things that might happen in the future would have a heightened perception of risk."

The researchers surveyed 95 African-American women who had a personal and family history of breast cancer that was suggestive of hereditary disease, had been treated for the disease with either lumpectomy or mastectomy, and had one intact breast. All of the women were offered the opportunity to participate in genetic counseling.

The researchers found that 53 percent of respondents felt they had the same or a lower risk of developing breast cancer again compared to other women, but that a substantial minority of the survivors (47 percent) reported that they had a higher or much higher risk.

Investigators found support for one of their hypotheses -- that women with more education were significantly more likely to perceive a higher risk of breast cancer recurrence.

But their hypothesis about time perception was wrong. Instead, perception of risk was related to how often a woman thought about the past. Women who thought more about the past were about three times more likely to report that they had a high risk of developing breast cancer again.

That finding makes sense, Halbert said, if respondents have a continued sense of vulnerability. "Because past experiences with disease may still be salient to women who think about the past a lot, these women may be likely to believe that they have a high risk of developing breast cancer again," she said.

The findings suggest that during genetic counseling, more focus should be placed on providing cancer risk information and in understanding the basis of risk perceptions, especially how they may be related to past experiences with disease, Halbert said. "We can enhance genetic counseling if we develop a better understanding of why women believe they may be at higher or lower risk," she said.

The study was funded by a grant from the Department of Defense.

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:

Greg Lester
267-646-0554
lester@aacr.org

Scientists Identify Pancreatic Cancer Stem Cells

registration@aacr.org () — Thu, 01 Feb 2007 12:00:00 GMT

Findings Bolster Theory That Stem Cells Are at the Root of Cancer

PHILADELPHIA - Researchers at the University of Michigan Medical Center have, for the first time, identified human pancreatic cancer stem cells. Their work indicates that these cells are likely responsible for the aggressive tumor growth, progression, and metastasis that define this deadly cancer.

In the February 1 issue of Cancer Research, the researchers demonstrate that only 100 of these stem cells are needed to produce human pancreatic cancer in half of mice tested. They also found these cells are at least 100 times more tumorigenic than cancer cells that did not have one of three protein markers they believe to be associated with pancreatic cancer stem cells.

The findings could help advance development of new therapies for this cancer, which has a five-year survival rate of only three percent - the worst prognosis of any major cancer, said the study's lead author, Diane M. Simeone, M.D., an associate professor of surgery and molecular and integrative physiology.

"The cells we isolated are quite different from 99 percent of the millions of other cells in a human pancreatic tumor, and we think that, based on some preliminary research, standard treatments like chemotherapy and radiation may not be touching these cells," said Simeone. "If that is why pancreatic cancer is so hard to treat, a new approach might be to design a drug that specifically targets pancreatic cancer stem cells without interfering with normal stem cell function."

While such a drug has not been developed, ongoing research suggests it is possible to do so, she added.

The study also advances the emerging notion that stem cells may lie at the heart of some, if not all, cancers, Simeone said. That theory suggests that only cells that have the properties of "stemness"- that is, cells that can self-renew and differentiate into other types of cells - are the only ones capable of producing tumors. These "cancer stem cells," could derive from normal adult stem cells in organs that have mutated, or from a differentiated cell that has devolved to take on the qualities of stem cells. They are resistant to traditional therapy designed for cells that rapidly turn over because stem cells don't, according to some researchers. Thus, they remain after tumors shrink and may be responsible for cancer recurrence and metastasis.

This study confirms at least one of those concepts, the researchers said. "Our study demonstrates that the very small subset of cells in a human pancreatic tumor that cause the cancer to grow and propagate have stem cell-like features," Simeone said.

To look for cancer stem cells in pancreatic cancer, the research team implanted cancerous tissue from human pancreatic specimens removed during patient surgery in "xenograft" mice with compromised immune systems. Researchers removed tumors after they grew, and then sorted millions of cancer cells to isolate those that had one or more of three surface protein markers - CD44, CD24, and ESA. They chose these markers, called cell adhesion molecules, because they'd recently been found on isolated breast cancer cells by study co-authors Max Wicha, M.D., from Michigan and Michael Clarke, Ph.D., from Stanford University School of Medicine.

The researchers then implanted about 100 of each type of cell in mice, and found that tumors would grow in a subset of the animals, but cells that expressed all three markers were the most potent, producing tumors in six of 12 mice tested. If more cells are used, "we can get tumors to grow 100 percent of the time," Simeone said. "These cells are highly tumorigenic, which reflects the biology of this cancer."

Additionally, the tumors derived from the highly tumorigenic pancreatic cancer cells "appeared remarkably similar to the appearance of tumors taken directly from patients," Simeone said. The purported cancer stem cells produced a diverse mixture of cells, some of which are not cancerous, that reflected an actual human pancreatic tumor, she said.

The markers that define the highly aggressive pancreatic cancer subtype are not identically matched to those found in aggressive breast cancer, the researchers also discovered. The difference is in one marker, CD24, which is negative in breast cancer and positive in pancreatic cancer, according to Simeone.

"These studies suggest that several stem cell markers may be shared by cancer stem cells in different tumor types, such as CD44 and CD133, but it is possible that each tumor cancer stem cell has its own set of unique markers," Simeone said.

The study was funded by the Lustgarten Foundation, the Els Pardee Foundation, the Michigan Life Sciences Corridor, and the American Diabetes Association.

Editors Note: To subscribe to the AACR press release distribution list please e-mail communications@aacr.org

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Study Finds Flaws in Cancer Clinical Trials

registration@aacr.org () — Thu, 01 Feb 2007 12:00:00 GMT

PHILADELPHIA - Cancer research and drug development are yielding more sophisticated candidate therapies, but investigators' methods to test them haven't kept pace, according to researchers at Memorial Sloan-Kettering Cancer Center. That could explain why so many experimental drugs fail in the final large and costly phase of testing, they say.

In the February 1 issue of Clinical Cancer Research the researchers found that only nine of the 70 Phase II studies they examined clearly defined measures by which an experimental drug could be judged to offer benefit to patients.

"We are facing a new and growing problem in clinical trial testing, and that is while the drugs have changed, researchers are still using the same old methods to gauge how effective they are," said the study's lead author, Andrew Vickers, Ph.D., a research methodologist.

The problem, Vickers said, is that for so long, therapies (usually chemotherapy) were tested by seeing if tumors would shrink in patients with advanced cancer. Measuring that reduction was an accepted way to gauge benefit, he said. But today's new treatments, which can include targeted therapies that slow tumor progression, are often tested in less advanced cancer and in combinations "and it can be hard to answer the question of whether patients are doing better than expected," he said.

In their study, Vickers, Howard Scher, M.D., Chief of the Genitourinary Oncology Service, and medical student Vennus Ballen, examined Phase II clinical trials reported from June 2003 - June 2005 in the Journal of Clinical Oncology or in Cancer, two major journals in cancer research. These studies, which usually enroll 30 to 50 patients, aim to provide a "go/no go" decision on whether the therapies studied should be evaluated in a large Phase III clinical trial, the ultimate test of whether a drug should be given to cancer patients.

They specifically looked at 70 studies whose design required "historical data" to determine whether a drug was promising enough to justify a Phase III trial. "When a novel agent is added to an existing standard in the hope of increasing response rates over and above those expected from the standard treatment alone, historical data on the response rates to the standard treatment are required," Vickers said. "Similarly, some agents are thought to slow disease progression, rather than lead to rapid tumor regression, necessitating an endpoint such as progression-free survival or overall survival at one year. That survival target clearly needs to be developed by reference to historical data."

For example, if two chemotherapy drugs used in combination lead to a 30 percent survival rate at one year, and researchers are interested in knowing whether an addition of a third drug is of benefit, the three-drug combination has to meet that 30 percent hurdle and jump over it, Vickers said. "So we have to be pretty certain that the 30 percent target is correct," he said.

Of the 70 studies they examined, however, nearly half (46 percent) did not give any justification for the historical target. And of the studies that did refer clearly to prior data, only a few (nine, or 13 percent), did so properly. Furthermore, trials that failed to report a rationale for the historical bar were much more likely to conclude that the new therapy was "active" and therefore worthy of further study or a Phase III clinical trial, Vickers said.

The researchers could not find a single study that used advanced statistical techniques to adjust for differences between patients studied in older clinical trials that were used as the historical bar and patients treated in the new trial, who may be at an early stage of cancer.

"These studies could have been done better", Vickers said. "Phase II studies are all about seeing whether patients on a new treatment are doing better than expected; if so, we should investigate the new treatment in a really big trial."

"However, to know whether we are 'doing better than expected' we need some kind of benchmark of what we should expect from standard treatment," Vickers said. "That benchmark assessment is what we find is missing from these studies."

The study was funded by the National Institutes of Health.

Editors Note: To request a PDF of this article please e-mail decicco@aacr.org or ortiz@aacr.org. To subscribe to receive AACR press releases please e-mail communications@aacr.org

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Peptide Vaccine Fights Off Breast Tumors with Aid of Bacteria-Mimicking Agents

registration@aacr.org () — Thu, 01 Feb 2007 12:00:00 GMT

PHILADELPHIA -- With the help of immune system-stimulating molecules that mimic bacterial components, researchers have used a type of cancer vaccine to both delay and prevent breast tumors in mice. The strategy, they say, holds promise for the future use of peptide vaccines in women who are at high risk for developing breast cancer.

Researchers from the Mayo Clinic, University of South Florida, and University of Torino employed substances called toll-like receptor agonists to help a synthetic peptide vaccine raise the immune system response against breast cancer tumors. Simultaneously, they used antibodies to blunt other aspects of the immune system that might interfere with a strong killer T cell response, improving the effectiveness of the vaccine.

In the February 1 issue of Cancer Research, the researchers report that their strategy was effective in preventing spontaneous tumors in transgenic mouse models for breast cancer, even when the vaccine was given when the mice already had early stage cancer.

"The challenge is to get a foreign peptide recognized by the immune system as a threat so it can react and produce anti-tumor immune cells," said Esteban Celis, M.D., Ph.D., professor in the department of interdisciplinary oncology at the H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida in Tampa. "We've shown that stimulating the immune system using toll-like receptor agonists is very important to alerting it and producing lymphocytes that will have an anti-tumor effect."

According to Celis, the immune system usually doesn't react as strongly to a synthetic peptide in a vaccine as it does against an infectious agent, which is why immune system boosters such as toll-like receptor agonists, which mimic bacterial DNA, help. They also used anti-CD25 antibodies to tie up immune system T regulatory cells, which often serve as brakes that can reduce responses to the vaccine.

The researchers studied both normal mice and transgenic mice carrying an activated HER2/neu oncogene, which has been linked to breast cancer in humans. In order to get a protective immune response, the transgenic mice were repeatedly given vaccine in combination with the toll-like receptor agonist or were given antibodies that blocked their protective T regulatory cells. Celis and his colleagues found that the peptide vaccine administered this way could prevent or slow the growth of injected tumor cells, and showed some benefit against early stage spontaneous breast tumors.

The vaccine was most effective in preventing spontaneous tumors when it was given once at week eight - along with anti-CD25 antibodies -- when most mice have excessive and often precancerous breast tissue growth called hyperplasia. It completely prevented spontaneous tumors in HER2/neu mice up to 35 weeks of age. Even without the antibody, tumors took much longer to develop, and when they did, they grew more slowly.

"This kind of therapy could be applied to women who have a high likelihood of developing cancer -- women with pre-malignant hyperplasia or who have a genetic predisposition or make-up that makes them at high risk," Celis said.

Although the peptide vaccine was effective in preventing spontaneous tumors in the HER2/neu mice, Celis cautions that the mice had to be vaccinated prior to the appearance of measurable tumors and that the animals had to receive repeated immunizations.

"Once tumors appear, only certain mice respond and there is only a delay in tumor growth," he said. "It extends survival but does not cure the mice. We know that the immune response in these mice is much lower than in the animals that are younger, and it's likely that the tumor is making something that is inhibiting the immune response."

###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

CONTACT:
Greg Lester
267-646-0554
lester@aacr.org

Simple Diagnostic Test Detects Genetic Signs of Lung Cancer in Patient's Sputum

registration@aacr.org () — Thu, 18 Jan 2007 12:00:00 GMT

PHILADELPHIA- DNA coughed up along with phlegm could point to lung cancer, say researchers at the University of Maryland School of Medicine who are developing an inexpensive and non-invasive gene probe to help diagnose early stage lung cancer in current and former smokers.

In the January 15 issue of Clinical Cancer Research, the researchers report that their fledgling test, designed to check whether two genes believed to be tumor suppressors are deleted in cells found in sputum, identified 76 percent of stage I lung cancer patients whose tumors also showed the same genetic loss. Existing sputum "cytology" tests, which look for changes in cell structure, identified only 47 percent of the patients, they say.

While no other simple sputum analysis has found such a high correlation with lung cancer, it is not yet good enough for the clinic, researchers say, and so they are now expanding their test to screen for up to eight genes.

"There is an urgent need to develop reliable early diagnostic biomarkers for lung cancer that can be detected non-invasively, and these two genes look to be great candidate markers for such a test," said Feng Jiang, M.D., Ph.D., assistant professor of pathology at the University of Maryland School of Medicine. "We need to validate our findings, of course, but we have shown that the genetic aberrations seen in sputum reflect the same genetic aberrations found in lung tumors, and that these molecular changes occur before any morphological changes can be seen in a cytology test."

Sputum cytology is still used in some clinics, but has largely been found to be insensitive, Jiang said. For that reason, he and his collaborators have been working for years on a simple, effective way to detect changes in the genes of cells in the bronchial airway that signify early cancer is developing somewhere in the lung system. Many cells within the airway exhibit a similar pattern of genetic abnormalities that leads to lung cancer development, the researchers say, but the challenge is to find altered genes that are only predictive of cancer, and not just of general cellular damage from smoking.

"Most heavy smokers never develop lung cancer, even though cells in their airways show genetic damage," Jiang said. "The trick is to find the genes that are only cancer related."

The research group had previously identified a set of genes that were deleted in lung cancer tumors, and in this study, they tested three of them (HYAL2, FHIT, and SFTPC) in sputum samples taken from 38 patients with stage 1 non-small cell lung cancer, 36 cancer-free smokers and 28 healthy nonsmokers.

Given that sputum contains expectorated airway cells, the researchers asked each of the participants to cough into a cup first thing in the morning for three days. Investigators then examined the sputum with both traditional cytology and with fluorescent in situ hybridization (FISH). The FISH technique uses fluorescently labeled single-strand DNA probes to bind to the complementary strand of a specific gene. The presence, or absence, of a fluorescent signal produced when the strands bind can be detected and scored with use of a special microscope.

"As a diagnostic tool to identify early stage lung cancer patients who would then benefit most from curative therapies, FISH is very cheap and convenient," Jiang said. "The technique may be also useful in monitoring lung cancer patients for response to treatment, disease progression and early evidence of relapse in the future."

They found that FISH could not detect deletions in the SFTPC gene in sputum, although it was absent in 71 percent of tumors. But the loss of HYAL2 and FHIT in a patient's tumor could be detected in that person's sputum. The investigators specifically found that HYAL2 and FHIT were deleted in 84 percent and 79 percent of tumors and in 45 percent and 40 percent of matched sputum, respectively. Combining both HYAL2 and FHIT deletions increased sensitivity to 76 percent (compared to 46 percent for cytology tests) and the combined probe had a specificity of 92 percent.

The false positive rate of about eight percent occurred because HYAL2 was found in sputum of four cancer-free smokers and FHIT deletions was found in three cancer-free smokers. However, the deletions were not found in the sputum of healthy non-smokers. "Those deletions in cancer-free smokers could represent an early indication that lung cancer is developing that has not yet been detected, but we won't know that without longer follow-up study," Jiang said.

The study was funded by the National Cancer Institute, and a researcher from The University of Texas M. D. Anderson Cancer Center participated with University of Maryland investigators in the study.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
267-646-0554
lester@aacr.org

Selective Marker Found to Indicate Aggressive Form of Breast Cancer

registration@aacr.org () — Mon, 15 Jan 2007 12:00:00 GMT

PHILADELPHIA- Researchers have linked a structural protein called nestin to a particularly deadly form of breast cancer, identifying a new biomarker that could lead to earlier detection and better treatment.

In the January 15 issue of Cancer Research, researchers from Dartmouth Medical School demonstrate that nestin could represent a selective biological marker for basal epithelial breast tumors, a highly aggressive cancer with similarities to mammary stem cells, the regenerative cells believed to be the site of breast cancer initiation.

"Patients with this type of breast cancer are at high risk for recurrence," said James DiRenzo, Ph.D., assistant professor at Dartmouth Medical School. "Ideally, a marker like nestin would enable clinicians to monitor these patients through frequent tests of a biomarker and, in doing so, detect the cancer before it has a chance to come back."

Basal epithelial tumors lack important molecular targets such as the estrogen receptor, progesterone receptor and Her2. This not only makes positive diagnosis difficult, say researchers, but also eliminates several important lines of therapy, such as tamoxifen or Herceptin, that work well for other breast cancer subtypes.

"Currently, there is no direct means of determining if a breast cancer is a basal epithelial tumor - doctors only know for certain once the other forms of breast cancer are ruled out," DiRenzo said. "This type of breast cancer is generally difficult to manage, but several important studies have shown that it is more likely than other breast cancer subtypes to respond to certain types of therapy, which highlights the need for a definitive diagnostic marker."

The basal epithelial breast cancer subtype represents 17 to 37 percent of all breast cancers and is more common in premenopausal African American women than in other demographic groups. Among breast cancers, this subtype is known to have an early age of onset and a very short time between treatment and relapse. It is more commonly detected during normal screening mammogram intervals than other screening subtypes, which likely reflects its aggressive nature. These important clinical correlations likely explain why this subtype disproportionately accounts for breast cancer mortality, according to DiRenzo.

In a retrospective study of breast cancer tumors lacking estrogen receptors, progesterone receptors and Her2, DiRenzo and his colleagues found extremely high amounts of nestin in 14 of 16 tumor samples examined. While the researchers plan to strengthen their findings with a larger prospective study, their results offer a crucial first step in diagnosis and management of a disease that is notoriously difficult to control. Consistent with other studies showing that breast cancers associated with inherited mutations in BRCA1 display the basal phenotype, DiRenzo and colleagues found high levels of nestin in these tumors as well.

Nestin is a long filamentous protein found in adult stem cells in the central nervous system. While scientists do not know its exact function, the protein is thought to have a role in stabilizing the structure of adult stem cells as they regenerate and divide into daughter cells.

"Normal basal epithelial tissue produces nestin, but basal epithelial tumors produce a tremendous amount of nestin, which likely represents an abnormal expansion of the basal epithelia." DiRenzo said. "If it is indeed specific to regenerative cells, then it will make for an excellent diagnostic tool for a cancer of regenerative mammary cells."

According to the DiRenzo, another important next step will be finding an efficient means of detecting nestin in a clinical screening setting. While it seems unlikely that a blood test would be sufficient, DiRenzo believes that a non-invasive test that collects samples from mammary ducts may enable the development of a screening tool for at-risk patients.

The study was funded by the National Cancer Institute, the U.S. Department of Defense Breast Cancer Research Program and the Mary Kay Ash Charitable Foundation.

# # # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Contact:
Greg Lester
(267) 646-0554
lester@aacr.org