Press Releases: 2006

Pair of MicroRNA Molecules Controls Major Oncogene in Most Common Leukemia

registration@aacr.org () — Fri, 15 Dec 2006 12:00:00 GMT

PHILADELPHIA - Researchers at Ohio State University have discovered that two microRNA (miRNA) molecules help control the oncogene responsible for a dangerous form of B-cell chronic lymphocytic leukemia (B-CLL), the most common human leukemia in the world.

Their findings, published in the December 15 issue of Cancer Research, demonstrate that miRNAs are emerging as powerful regulators of gene expression in cancer development, and could offer new targets for drug treatment, the investigators say.

In this case, high levels of two miRNAs known as miR-29 and miR-181 seem to suppress expression of the TCL1 oncogene that drives the most aggressive forms of the leukemia, said the study's lead author, Yuri Pekarsky, Ph.D., assistant professor in the Department of Molecular Virology, Immunology and Medical Genetics at Ohio State University's Comprehensive Cancer Center.

"We have found a direct inverse association between expression of miR-29 and miR-181 and that of the TCL1 oncogene," he said. "It works in both directions. High expression of these miRNAs correlates with low expression of TCL1, in the indolent form of cancer that is less likely to progress. A low level of miR-29 and miR-181 is associated with a much more aggressive cancer."

Drugs that boost production of these two natural TCL1 inhibitors might work as a future treatment for B-cell chronic lymphocytic leukemia, he said. These molecules could also be combined with 12 other miRNAs known to be associated with B-CLL to provide a test that may help determine prognosis and treatment, he said.

Researchers at Ohio State have been leaders in characterizing the role of miRNAs in cancer development. These small molecules are single-stranded RNA molecules that can act either as tumor suppressors or oncogenes. They can block transcription of genes by stopping them from producing messenger RNA or can inhibit translation of the genes by blocking production of proteins from messenger RNA, according to Pekarsky. Earlier this year the investigators provided the first direct evidence that over-expression of an miRNA molecule could result in development of cancer have since identified a number of miRNAs associated with B-cell chronic lymphocytic leukemia that appear to promote tumor development.

But the protective miR-29 and miR-181 molecules are emerging as the most important miRNAs discovered to date, Pekarsky said. "MicroRNAs such as these could prove to be as powerful as the protein transcription factors that we know can turn genes on and off," he said.

The researchers studied TCL1 expression and miRNA expression in 23 samples of indolent B-CLL, 25 samples of aggressive B-CLL, and 32 samples of B-CLL exhibiting a chromosomal deletion, which makes it the most difficult type to treat. They found that TCL1 over-expression correlated with the two most aggressive forms of the cancer. To determine which miRNAs targeted TCL1, they used microRNA-microchips and elaborate computer programs to identify miR-29 and miR-181.

Regulation of TCL1 expression by these two miRNAs is relevant to all the three groups of cells studied, Pekarsky said. "You can look at the miRNA profile and say whether the cancer is aggressive or indolent," he said. And of the two miRNAs, miR-29 offers the most predictive power, Pekarsky added.

"We have a lot of work to do to characterize these miRNAs because we don't even know whether they work on transcriptional or translational level," he said. "But finding that they control this cancer's major risk factor is a very helpful advance."

The study was funded by the National Institutes of Health, among other grants. Researchers from the University of California at San Diego also contributed to 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:

Staci Vernick Goldberg
215-440-9300 ext. 145
goldberg@aacr.org

Researchers Find Two Biomarkers with Potential to Predict Breast Cancer Spread

registration@aacr.org () — Fri, 15 Dec 2006 12:00:00 GMT

PHILADELPHIA - Expression of two different proteins taken from primary tumor biopsies is highly associated with spread of breast cancer to nearby lymph nodes, according to researchers who say this protein profile could help identify at an early stage those patients whose disease is likely to metastasize.

In the December 15 issue of Cancer Research, the researchers say over-expression of one unidentified protein and under-expression of another is 88 percent accurate in identifying breast cancer that has spread in a group of 65 patients, compared to an analysis of lymph nodes and outcomes.

If the predictive and diagnostic power of these proteins is validated, they could be analyzed in primary tumor biopsies that are routinely collected at the time of diagnosis, saving some women from extensive and possibly unnecessary treatment as well as from undergoing a second surgery to collect lymph nodes for analysis, the researchers say.

"We want to be able to predict, at the earliest stages, if a tumor has spread and how dangerous it will be," said the study's lead author, Dave S. B. Hoon, Ph.D., director of Molecular Oncology at the John Wayne Cancer Institute, Saint Johns Health Center, in Santa Monica, California. "These two proteins may allow us to target aggressive tumors with more extensive therapy management to some women, while sparing others from needless treatment."

"Our approach is not to rely on hunting for lymph nodes during surgery, which will then only tell you whether the nodes are positive or negative, but to look at the primary tumor to predict how aggressive the cancer is at early stages," Hoon said.

The lymph system collects the fluid that surrounds tissue cells, which is then processed by nearby draining lymph nodes, so checking these nodes for the presence of cancer is currently one of the most important prognostic factors predicting breast cancer survival, he said. "One of the best predictors of systemic cancer spread is whether the draining lymph node has any signs of metastasis," he said.

Biopsy of this "sentinel" node occurs after the tumor has been removed in an initial surgery, and if metastasis is found there, surgeons continue to sample "downstream" nodes to check for degree of spread. While this procedure, called "sentinel node biopsy" is now practiced routinely in the U.S. and in many other countries, there remains controversy in the accurate assessment of micrometastasis in sentinel lymph nodes, according to Hoon. He said recent studies have found that it can produce both false positive and false negative results.

Furthermore, microdisease seen in the sentinel lymph node doesn't always predict that a patient will go on to develop metastatic breast cancer, said Hoon. "If the primary tumor and nodes are removed in some women, they will not develop recurrent disease, but in other women, removal of the nodes may have no impact on the spread of the metastatic disease that has already occurred prior to surgery."

In this study, 65 patients with invasive cancer who underwent surgery and biopsy of the sentinel lymph node and/or other lymph nodes were enrolled, and investigators were blinded as to the findings of these lymph node biopsies.

In all, 24 patients (37 percent) were found to have cancer in their nodes and 41 patients (63 percent) were node negative. To predict lymph node metastasis, the investigators used a ProteinChip^TM to identify biomarkers that distinguished between the tumor profile with paired positive and negative nodes.

Two protein peaks associated with lymph node metastasis were identified. Specifically, over-expression of protein peaks at 4,871 Da (which represents the molecular weight of the protein) and under-expression of a protein peak at 8,596 Da were highly predictive of lymph node metastasis.

Patients with two or more positive lymph nodes were significantly more likely to show over-production of 4,871 Da, compared to patients with no lymph node spread. The peak at 4,871 could also predict patients with four or more metastatic nodes who have significantly worse outcomes.

Although they don't know what these proteins are, by searching a protein database Hoon suggests that 4,871 Da may represent thymosin beta-10, a peptide that has already been associated with out-of-control growth and cell differentiation, and that 8,596 Da could represent an ubiquitin protein associated with a good prognosis in node-negative breast cancer.

"Protein peaks found in our study may be useful as prognostic biomarkers, but we must be cautious until the identities of these proteins are known and validated in a larger study," Hoon said.

The study was funded by the California Breast Cancer Research Program of the University of California, the Avon Foundation, and the Leslie and Susan Gonda Foundation. Investigators from Saint John's Health Center, Joyce Eisenberg Breast Center, in Santa Monica also contributed to 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:

Staci Vernick Goldberg
215-440-9300 ext. 145
goldberg@aacr.org

Smokers Who Cut Back on Cigarettes May Negate Benefit through "Compensatory Smoking"

registration@aacr.org () — Mon, 11 Dec 2006 12:00:00 GMT

PHILADELPHIA - Heavy smokers who have reduced their number of daily cigarettes still experience significantly greater exposure to toxins per cigarette than light smokers, according to a new study by researchers at the University of Minnesota.

Even when smokers in the two groups smoked as few as five cigarettes a day, heavy smokers who reduced their cigarette intake experienced two to three times the amount of total toxin exposure per cigarette when compared with light smokers, researchers report in the December issue of Cancer Epidemiology, Biomarkers & Prevention.

In addition, researchers observed that the more that heavy smokers reduced their smoking, the more likely they were to increase their exposure to toxicants per cigarette presumably because they took more frequent puffs or inhaled deeper or longer on each cigarette, a process referred to as "compensatory smoking." As a result, smokers who decreased their smoking to as little as one to three cigarettes per day experienced a four- to eight-fold increased exposure to toxins per cigarette as compared with light smokers.

Compensatory smoking occurs because smokers are trying to maintain a specific level of nicotine in their bodies, says Dorothy K. Hatsukami, Ph.D., lead author of the study and director of the University's Transdisciplinary Tobacco Use Research Center in Minneapolis. Other factors, such as the sensory aspects of smoking, also may play a role in compensatory smoking, Hatsukami says.

"These results are consistent with other studies that show that people who decrease their smoking by 50 percent or more don't experience a comparable reduction in risk for lung cancer because they tend to smoke their fewer cigarettes more intensely," she says. "The best way to lower the risk for premature death is to stop smoking altogether."

For the study, Hatsukami and colleagues compared a group of 64 people participating in two smoking reduction intervention studies and who reduced their smoking to levels similar with a group of 62 light smokers. The researchers created a mathematical formula to calculate the degree of smoking compensation in reducers compared with light smokers. As part of the formula, they measured a biological marker, total NNAL, which indicates the amount of exposure to the tobacco-specific lung cancer-causing agent NNK.

The light smokers averaged age 48, were 53 percent female and smoked an average of 5.6 cigarettes a day. The reducers averaged age 51, were 39 percent female and smoked an average 26 cigarettes per day prior to cigarette reduction. All of the reducers studied decreased their smoking by at least 40 percent and smoked five cigarettes per day within six months of enrolling in the study.

Results indicated that the average level of NNAL for reducers was more than twice that of light smokers, even when the two groups smoked about the same number of cigarettes per day. The amount of smoking reduction was shown to be a strong predictor of compensatory smoking, with greater cigarette reduction associated with more compensation.

Hatsukami says heavy smokers fare better health-wise by quitting smoking than decreasing their cigarette intake: "Although light smokers have lower levels of disease risk than heavy smokers, a low rate of smoking still confers increased risk compared to non-smokers and quitters."

In a previous study of smoking reduction using nicotine replacement therapies such as gum or patches, the researchers observed that smokers who reduced their cigarette intake by 73 percent only experienced a 30 percent reduction in carcinogens because of compensatory smoking. Another study showed that a reduction of 62 percent in tobacco consumption was associated with only a 27 percent reduction in lung cancer risk.

The research was supported by the National Institute on Drug Abuse.

# # # #

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:
Staci Vernick Goldberg
215-440-9300 ext. 145
goldberg@aacr.org

Exercise Can Reduce a Smoker’s Lung Cancer Risk, but Quitting Smoking Is Still Most Important

registration@aacr.org () — Mon, 11 Dec 2006 12:00:00 GMT

PHILADELPHIA - In a study of more than 36,000 women, researchers observed that smokers can reduce their risk of developing lung cancer by being physically active. However, they strongly caution that any relative benefit is dwarfed by the benefits gained from quitting smoking.

The researchers, from the Universities of Minnesota and Pennsylvania, report in the December issue of Cancer Epidemiology, Biomarkers & Prevention that a high level of physical activity in women who smoked reduced their relative risk of developing lung cancer by 28 percent.

While this may sound like welcome news to female smokers who don't want to quit, the investigators emphasize that the absolute risk of developing lung cancer is still much greater in current and former smokers regardless of activity level.

"The most important thing a smoker can do to reduce risk is to quit smoking. That said, exercising and being active can offer a marginal change in risk," said the study's lead author, Kathryn Schmitz, Ph.D. an assistant professor at the University of Pennsylvania. Schmitz worked on the study with a team of researchers while on faculty at the University of Minnesota.

In other words, she says, a physically active smoker has a 35 percent lower risk of lung cancer than a sedentary smoker, but if both smokers quit, they would both reduce their risk by as much as 10- or 11-fold. "Smokers who exercise are at a 35 percent lower risk of developing lung cancer relative to smokers who don't exercise, but if you smoke at all, your risk of developing lung cancer is 10- to 11- fold higher than if you didn't smoke."

"The helpful message from this study is that if a smoker is having trouble quitting, exercise can be a first step toward better health," says Schmitz.

The findings were derived from the Iowa Women's Health Study, which in 1986 began to follow almost 42,000 women between the ages of 55 and 69. Over the years, five questionnaires were sent to the participants who recorded their smoking status and physical activity among other variables. This analysis, which began in 2002, included 36,410 participants, including 777 women diagnosed with the cancer. Among this group, 125 were non-smokers, 177 were former smokers, and 475 were current smokers.

Compared to women who were physically active, women with a low physical activity level at the baseline analysis were more likely to smoke, less likely to have a high school education and more likely to be obese.

Among smokers, the most number of cancer cases (324) were seen among women who currently smoked and had low activity, and the lowest number (40) was in the group of women who formerly smoked and were highly active. Compared to never smokers, current and former smokers had proportionally more squamous cell and small-cell lung cancer, which can be harder to treat than other subtypes.

Researchers don't know why activity could lower lung cancer risk, but suggest that improved pulmonary function may reduce both the concentration of carcinogenic particles in the smoker's airway and the extent to which they are deposited in the lungs. They also theorize that exercise training improves immune function and reduces the inflammatory responses that can impact cancer development.

"This may be useful information for smokers who are not currently willing to attempt smoking cessation or have recently failed a quit attempt," says Schmitz. "But even if there was a significant risk reduction, quitting smoking is unarguably the most important action a person can take for reduction of lung cancer risk."

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:

Staci Vernick Goldberg
215-440-9300 ext. 145
goldberg@aacr.org

Successful Lung Cancer Surgery Not Enough to Break Nicotine Dependence in Many Smokers

registration@aacr.org () — Mon, 11 Dec 2006 12:00:00 GMT

PHILADELPHIA - A new study has found that close to half of 154 smokers who had surgery to remove early stage lung cancer picked up a cigarette again within 12 months of their potentially curative operation, and more than one-third were smoking at the one year mark. Sixty percent of patients who started smoking again did so within two months of surgery. The study, led by researchers at Washington University School of Medicine and published in the December issue of Cancer Epidemiology, Biomarkers & Prevention, is the first to look at smoking relapse among people who were "forced" to quit due to impending surgery.

"These patients are all addicted, so you cannot assume they will easily change their behavior simply because they have dodged this particular bullet," said the study's lead author, Mark S. Walker, Ph.D., a clinical psychologist and Assistant Professor of Medicine at Washington University. "Their choices are driven by insidious cravings for nicotine."

The investigators found that those smokers who were the last to give up their cigarettes - some on the same day as their operation - and who saw smoking as a pleasurable activity they would have difficulty giving up, were also the first to resume the habit. And they concluded that patients who were able to hold out the longest before they took up a cigarette after surgery were the ones who were most likely not to be smoking in a year's time.

"The results suggest that patients who wait until cancer surgery to quit smoking need assistance from the medical community to help them stay away from cigarettes, and that this intervention should begin as soon as possible after treatment," Walker said. No such programs are currently offered to lung cancer surgery patients, he added.

At least seven studies of non-small cell lung cancer patients have shown that many of these patients continue smoking despite the risk, but the rate of relapse ranged from a low of 13 percent to about 60 percent. This study was unique in that it sought to include patients believed to be highly dependent on nicotine - so it included only patients who smoked within three months of their diagnosis - and it attempted to use saliva samples as well as questionnaires to gauge whether patients were smoking 3, 6, and 12 months after surgery.

Investigators at Washington University and at the University of Texas M.D. Anderson Cancer Center enrolled 154 patients being treated for early stage lung cancer at their centers. These patients were lucky, Walker said. "Their cancer was discovered largely by accident when they were being examined for other medical conditions, and so was potentially curable by surgery," he said. "More than two-thirds of lung cancer is diagnosed at later stages in people with symptoms, and treatment is much less successful."

The researchers found that 43 percent of patients smoked at some point after surgery and 37 percent were smoking 12 months after their operation.

Consistent with previous research, the investigators hypothesized that greater nicotine dependence, a younger age, lower income, and a lower level of education would be associated with a greater likelihood of smoking post surgery.

But that is not what they saw on two of the four variables. Instead, researchers found no link between the quantity of smoking and the ability to quit, and they also were surprised to discover that higher education was associated with a greater likelihood of smoking after surgery. "It wasn't the number of cigarettes smoked daily that determined who couldn't quit, but how long they continued to smoke before surgery. About half of the patients studied smoked within two weeks of their operation," Walker says. "We are not certain what to make of the finding about education, because no other study about smoking cessation has reached that conclusion."

How long patients quit before surgery may have been influenced by their "self efficacy" for quitting, he says. "The thing that really drove whether or not people relapsed is whether they saw smoking as pleasurable and rewarding to the point that they can't do without cigarettes, and they don't believe they are able to quit."

Patients who were able to quit by the one year mark waited longer to attempt to smoke again, or never began again. In fact, more than one in four patients who smoked after surgery were nonsmokers at the 12-month follow-up, he said. "Perhaps for these patients, lung cancer surgery was a wake-up call to quit, but many others need intervention to help them fight nicotine."

The study was funded by grants from 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 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:

Staci Vernick Goldberg
215-440-9300 ext. 145
goldberg@aacr.org

RSS Feeds Now Available for AACR Journals

registration@aacr.org () — Wed, 29 Nov 2006 12:00:00 GMT

RSS Feeds Now Available for AACR Journals

The tables of contents and abstracts of AACR journals are now available in RSS format. Subscribe to journal feeds and have the contents of each issue delivered to your RSS reader. Click on the journals links below to subscribe. Download the Guide to Using RSS Feeds for more information.

NCI Scientists Launch Spotlight on Molecular Profiling

registration@aacr.org () — Mon, 20 Nov 2006 12:00:00 GMT

Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and their colleagues today introduced a new series of research articles, "Spotlight on Molecular Profiling," in the November 7, 2006, issue of Molecular Cancer Therapeutics*. The series will highlight molecular profiling studies that provide broad-spectrum genomic and proteomic data that could prove useful for the discovery of new drugs and biomarkers. The first article published in the series shows how such profiles can be used to discover a new biomarker that might someday help to personalize treatment of ovarian cancer. This study, as well as a commentary on molecular profiling, opens the series.

"Rather than forming a hypothesis about a specific gene or protein and designing experiments to test it, molecular profiling takes a more global approach to cancer research," said NCI Director John Niederhuber, M.D. "This technique surveys the expression of thousands of genes in a single experiment to map the changes in the human genetic blueprint associated with cancer. The molecular profiling approach will accelerate our understanding of the molecular basis of cancer and will lead to new insights for the treatment, detection, and prevention of these diseases."

Cancer is a term that encompasses at least 200 different diseases characterized by genetic changes that alter the normal, controlled growth and division of cells. If cancer research in the pre-genomic era -- before the sequencing of the human genome -- was a cottage industry dedicated to the study of individual molecules and processes, then the post-genomic era is an industrial revolution. This new age is defined by technological advances, such as microarray platforms, that allow for the global, simultaneous study of the 20,000 to 25,000 genes that make up the human genome.

This new series of articles will examine and compare genetic profiles of different cancer types toward the goal of developing tools to personalize anticancer strategies.
"The real value of molecular profiling will be realized when biomedical scientists with a particular expertise are able to integrate and use the data fluently for hypothesis generation, hypothesis-testing, and what I would term 'hypothesis-enrichment'," said John Weinstein, M.D., Ph.D., head of the Genomics and Bioinformatics Group at NCI.

In one of the inaugural articles in the Spotlight series, Weinstein and his colleagues used a panel of 60 human cancer cell lines, known as the NCI-60 panel, to analyze the actions of L-asparaginase (L-ASP), a bacterial enzyme that has been used since the 1970s to treat acute lymphoblastic leukemia. L-ASP scavenges the blood, chewing up molecules of free asparagine, one of 20 amino acids needed to build proteins in a cell. Normal cells can use the enzyme asparagine synthetase (ASNS) to make their own asparagine, but L-ASP selectively starves cancer cells that cannot produce enough of the amino acid for their own needs.

Since recent studies have suggested a link between L-ASP activity and ASNS, the NCI research team analyzed activation of the ASNS gene in the NCI-60 cancer cell lines, the most extensively-profiled set of cells in existence. Each cell line originated from a single cell type taken from a cancer patient and was then transformed in the lab to grow indefinitely outside the body. The NCI-60 panel of cells has been used by NCI's Developmental Therapeutics Program to screen more than 100,000 compounds for anti-cancer activity since 1990.

To examine this relationship, the researchers used microarray analysis, a powerful technology that measures activation levels for thousands of genes at once. In this study, five different microarray platforms used in the molecular profiling of the NCI-60 revealed a strong correlation between the anticancer activity of L-ASP and reduced activation of the ASNS gene in ovarian cell lines. Subsequently, the researchers and their collaborators used RNA interference, a recently developed genetic technique, to reduce the activation level of ASNS five-fold in one of those cell lines. As a result, L-ASP became over 500 times more effective at killing the cancer cells, suggesting that ASNS levels are the principal determinant of L-ASP activity. Furthermore, this increased activity was maintained in ovarian cancer cells that had developed classical multi-drug resistance to other forms of treatment.

"We are hopeful that the level of ASNS expression may one day be useful as a tool for selecting ovarian cancer patients who will most benefit from the use of L-ASP," said Philip Lorenzi, Ph.D., NCI, lead author of the study. "This study provides an example of what the NCI-60 cell line panel can do that is complementary to a different NCI-sponsored study, The Cancer Genome Atlas, which is profiling clinical tumors."

The Cancer Genome Atlas (TCGA) is a three-year, 100 million dollar collaborative pilot project launched in December 2005 by NCI and the National Human Genome Research Institute, also part of the NIH. TCGA aims to use tissue samples derived from cancer patients to systematically explore the universe of genomic changes involved in several types of human cancers. Cell lines, including the NCI-60, are different from the clinical tumors that will be the focus of TCGA. Cell lines are unlimited in number, easy to manipulate, and valuable for repeating experiments under the same conditions, but they do not necessarily reflect all of the properties of tumors found in patients.

"This emphasis on molecular profiling reflects a shift in research from small-scale to large-scale efforts, which are necessary because the genetic changes that lead to cancer occur in the context of whole genomes. Not all genetic changes are the same, not all cancers are the same, and they should not be treated as such," said Weinstein.

###

* 1) Weinstein JN, et al. Spotlight on molecular profiling: ''Integromic'' analysis of the NCI-60 cancer cell lines. Molecular Cancer Therapeutics 2006; Online November 7, 2006.
2) Lorenzi PL, Reinhold WC, Rudelius M, Gunsior M, Shankavaram U, Bussey KJ, Scherf U, Eichler GS, Martin SE, Chin K, Gray JW, Kohn EC, Horak ID, Von Hoff DD, Raffeld M, Goldsmith PK, Caplen NJ, Weinstein JN. Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells. Molecular Cancer Therapeutics 2006; Online November 7, 2006.
3) Ikediobi ON, Davies H, Bignell G, Edkins S, Stevens C, O'Meara S, Santarius T, Avis T, Barthorpe S, Brackenbury L, Buck G, Butler A, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Hunter C, Jenkinson A, Jones D, Kosmidou V, Lugg R, Menzies A, Mironenko T, Parker A, Perry J, Raine K, Richardson D, Shepherd R, Small A, Smith R, Solomon H, Stephens P, Teague J, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Reinhold W, Weinstein JN, Stratton MR, Futreal PA, Wooster R. DNA sequence analysis of 32 known cancer genes in the NCI-60 cell lines Molecular Cancer Therapeutics 2006; Online November 7, 2006.

For more information on Dr. Weinstein's research and for a set of computer resources that include the databases and tools for integrating the data, go to http://ccr.cancer.gov/staff/staff.asp?profileid=5816

For more information on NCI's genomic approach to cancer research, go to Integromic Analysis of the NCI-60 Cancer Cell Lines The Cancer Genome Atlas
NCI's Division of Cancer Treatment and Diagnosis provides resources to interested researchers at http://dtp.nci.nih.gov

For more information about cancer, please visit the NCI Web site at http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

High HPV Concentrations Combined with Cigarette Smoking Significantly Raise Risks of Later Cervical Cancer

registration@aacr.org () — Fri, 17 Nov 2006 12:00:00 GMT

PHILADELPHIA - Cigarette smoking and concurrent infection with high levels of the virus associated with cervical cancer can increase cancer risk by as much as 27 times, according to a study published in the November 2006 issue of Cancer Epidemiology, Biomarkers & Prevention.

Anthony Gunnell, a medical biostatistician and epidemiologist and colleagues at the Karolinska Institutet in Stockholm reviewed the medical exams of women with non-invasive cervical cancer in situ (the most common type) and cancer-free women in one of the largest studies to date to examine the relationships between smoking and the human papilloma virus (HPV). The virus and smoking behavior have long been associated with the disease, but not enough evidence has come forth to determine how either may cause the disease.

Gunnell's study, in fact, suggests that both may create a biochemical synergy that propels the disease. The researchers looked at "Pap" smear examination data from 105,760 Swedish women and identified 499 women with cervical cancer in situ, along with 499 cancer-free women as controls. For these women, they compared their smoking behavior with concentrations (known as viral load) of HPV-16, the viral strain most associated with cervical cancer. The researchers found that a combination of high viral loads and smoking during the time they were initially examined resulted in very high risk of later cervical cancer.

"We were surprised to see this dramatically increased risk among women with high viral loads who smoked," Gunnell said.

Among their findings:

Women who smoked and had a high HPV-16 load during their first exam had a 27-fold increased risk of later cancer than women who smoked but did not have an HPV infection.
Women who were positive for HPV-16 (irrespective of amount of viral load) and were smokers had a 14-fold increased risk over women who were HPV-16 negative and smoked.
Nonsmoking women with high HPV-16 loads had just a 6-fold risk compared to HPV-negative nonsmokers.

"Our initial analyses centered on whether smoking was an independent risk factor for cervical cancer," said Gunnell. "Clearly, both exposures need to be present at the same time for there to be interaction.

"Our study would imply a synergistic action between HPV and smoking that would greatly increase the likelihood of women developing cervical cancer if they are HPV-positive smokers. This would put them in a risk group worthy of careful monitoring."

The study, which also may partly explain why some women may not get cervical cancer despite smoking behavior or being HPV-positive, had too few women with high viral loads for the researchers to declare both smoking and HPV, by themselves, caused the disease. But since it was one of the largest studies to examine this relationship, it strongly suggests directions that future research should take to explore a causative effect.

The researchers also found a relationship between smoking duration and cancer. "We found a statistically significant multiplicative interaction between the duration of smoking and HPV presence causing cervical cancer," Gunnell said. "One explanation for this interaction could involve the influence of smoking on persistence of HPV infection, probably due to localized immune suppression. Conversely, it could be related to the progression of neoplastic growth, since HPV and smoking appear to alter the levels of certain cytokines, which are involved in controlling abnormal cell growth. More likely, the combination of both mechanisms are contributory factors.

In any event, confirmation of an interaction between cigarette smoking and HPV in cervical cancer development is of vital importance to public health, considering the widespread exposure to the virus and cigarette smoking in young women at risk for the disease, he said.

Cervical cancer is one of the leading causes of cancer deaths worldwide, and death rates are particularly high in developing countries. Although rates of incidence and mortality have dropped by 50 percent in the past 20 years, out of the 9,700 women diagnosed just in the United States this year, 3,700 will die. Early diagnosis and treatments have helped curb mortality rates, but the disease still remains one of the world's deadliest. In addition, it remains more common among Hispanic and African-American women.

Gunnell's colleagues in the study included Trung Tran, Anna Torrang, Paul Dickman, Par Sparen and Nathalie Ylitalo, of the Karolinska Institutet. Juni Palmgren also is a faculty member at Stockholm University. Their work was supported by grants from the U.S. National Institutes of Health, the Swedish Cancer Society and the Danish National Research 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:
Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

New Vaccine Stimulates Colorectal Cancer Patient’s Immune Systems to Fight Cancerous Cells

registration@aacr.org () — Wed, 15 Nov 2006 12:00:00 GMT

PHILADELPHIA - British researchers have developed a vaccine that stimulates colorectal cancer patients' immune systems to fight cancerous cells.

In a clinical trial of 67 patients, researchers at the University of Nottingham observed that when the vaccines were administered before and after surgery to remove cancerous tumors, they helped stimulate immune cell production in up to 70 percent of patients. These results are published in the November 15 issue of Clinical Cancer Research.

"This is the first vaccine shown to stimulate TNF-alpha - an immune-system protein that is very effective at killing cancer cells," said Lindy Durrant, senior author of the study and professor of cancer immunotherapy at the university.

The vaccine works by stimulating the patients' immune response to generate infection-fighting white blood cells called T cells, which in turn produce immune system proteins called cytokines that destroy cancer cells. The antibody contained in the vaccine, called 105AD7, was cloned from a patient who survived seven years with liver metastases from colorectal cancer, Durrant explained.

"This is very unusual as most patients die within one year of getting liver metastases," she said. "I thought if this antibody had helped this patient, if we could clone it, it might help others."

105AD7 is structurally similar to CD55, a protein that attaches to sugar molecules and is overexpressed in colorectal cancer cells, protecting them from attack by the body's immune system. While low levels of CD55 occur in all cells exposed to the immune system, increased expression of the protein has been observed in multiple types of tumors, including up to 80 percent of colorectal cancers.

During the trial -- the largest to date looking at 105AD7 plus surgery -- 67 patients with colorectal cancer who were scheduled for surgery to remove their primary tumor were randomly assigned to receive either 100 micrograms of 105AD7 with a powder to help absorb the vaccine, 105AD7 along with BCG (a bacteria used to stimulate the immune system in cancer patients) during the first immunization and the powder in subsequent vaccinations, or no treatment. The patients, who had varying degrees of disease, averaged age 66. Twenty-eight patients had colon cancer while in 39 patients the primary tumor was located in the rectum.

Patients were immunized before surgery on the day they were recruited for the study, and again two weeks later if surgery had not yet been performed. The vaccines were continued three, six and 12 weeks after surgery, and then at three monthly intervals up to a maximum of 24 months after surgery. Blood samples were collected from the patients during recruitment, at surgery, and at the time of the three-, six- and 12-week post-operative immunizations. Additional blood samples were acquired one month after each subsequent immunization.

Laboratory tests of the blood samples indicated that a T-cell response against the vaccine was recorded in the majority of patients. The responses tended to have two peaks: one following the start of the immunization schedule and another several months later, after additional immunizations. About 70 percent of patients produced both TNF-alpha and GM-CSF - a protein that stimulates white blood cell production - in response to both the vaccine and to CD55.

"The immune responses to both the vaccine and CD55 were measurable, adding support to the use of CD55 as a target in cancer treatment," Durrant said.

Nineteen of the patients died during the follow-up period. Durrant and colleagues noted that the trial was not designed to study the effect of the vaccines on survival.

The research was supported by The Research Foundation Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond.

# # # #

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

Exercise, Aspirin Consumption, and Childbirth May Alter Cancer Risk

registration@aacr.org () — Tue, 14 Nov 2006 12:00:00 GMT

BOSTON - Personal choices, such as smoking and consumption of fatty foods, have long been linked to increased cancer risk. During recent years, scientists have been seeking to isolate a variety of lifestyle decisions that may stave off the onset of cancer or even reduce tumor formation in their early stages. The latest round of such studies, presented at the American Association for Cancer Research's Frontiers in Cancer Prevention Research Meeting, include the impact of exercise on colon cancer in men, how aspirin consumption may negate the harmful effects of eating flame-broiled meat, and a new link between child bearing and lung cancer.

Effect of a 12-month exercise intervention on apoptosis in colon crypts: a randomized controlled trial

Exercising six days a week reduces the risk of colon cancer in men, according to a study by the Fred Hutchinson Cancer Research Center in Seattle. The study, conducted by Kristin Campbell, Ph.D., postdoctoral fellow, Public Health Sciences, and her colleagues, illustrated the role of exercise in controlling abnormal cell growth in colon tissue.

In men who engaged in moderate to vigorous exercise (an hour a day, six days a week) for a year, more apoptosis (normal cell life and death cycles) was seen in crypt cells in the colon. These cells are indentations in the colon wall and are the wellspring of polyps and other abnormal growths that can result in colon cancer. A protein called bax that promotes apoptosis was seen in higher amounts in the crypt cells among male exercisers. No such differences were seen in women, regardless of their exercise routines. But some changes in apoptosis were seen even among men who exercised less, about four times a week.

"We saw a substantial increase in the potential for cellular apoptosis in areas of the colon most vulnerable to colon cancer," said Campbell. "The increase was most pronounced in men who exercised six hours a week. No change was seen in women, a finding that is consistent with our previous findings of altered proliferation in men, but not women. Therefore, physical activity may play a stronger role in colon cancer risk reduction among men than it does among women."

The researchers examined 101 men and 98 women in one of the first randomized clinical trials to test the effect of exercise on colon cancer. The participants either exercised or maintained their usual non-active lifestyle for one year. At the same time, researchers measured apoptosis by measuring the ratio of bax, the apoptosis promoter protein, to bcl-2, an anti-apoptotic protein. The researchers also determined where in the colon-crypt cells these apoptotic changes were occurring.

Cellular proliferation in the bottom of colon crypt cells is normal. But precancerous polyps (and ultimately, cancer) can develop when the crypt's cells proliferate too quickly. In that case, cells growing too fast creep up from the bottom and spill over the upper sides, resulting in the growths seen in cancer and its predecessors. The researchers previously found lower proliferation on the upper portions of crypt cells in exercising men, while no decreases were found in women or men who did not exercise.

Is the association between flame-broiled food, meat consumption, and breast cancer modified by N-acetytransferases and aspirin use?

By studying the eating patterns of 312 women with breast cancer and 316 who were cancer free in a prospective study, Kala Visvanathan, M.B.B.S., assistant professor of epidemiology at Johns Hopkins University, and colleagues found that women who eat flame-broiled foods more that twice a month may be at increased risk of breast cancer when compared to women who don't usually eat foods prepared that way.

The good news, however, is that taking aspirin negated the potentially harmful effects.

"We are not certain of the mechanism by which aspirin may be helping attenuate these risks. This is an area that further study should elucidate as we search for means to reduce the risk of breast cancer," said Visvanathan.

The researchers first sought to determine if differences in a women's ability to activate the cancer-provoking chemicals in flame-broiled meat, known as heterocyclic amines (HCAs), modified the risk of developing breast cancer.

The NAT2 enzyme, short for N-acteyltransferase, is involved with activating heterocyclic amines. Several genes control NAT2's ability to activate HCAs: slow NAT2 metabolizers tend to produce less active HCAs than fast NAT2 metabolizers. The study found that fast metabolizers who ate more flame-broiled food were more likely to develop breast cancer than slow metabolizers who never ate such food.

"Previous work examining the association between NAT2, flame-broiled food, and breast cancer risk has been inconsistent. We find the relationship between aspirin, flame-broiled food consumption and NAT2 activity intriguing," said Visvanathan.

Nonsteroidal anti-inflammatory drugs and breast cancer risk: the multiethnic cohort

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) had little effect on reducing the risk of breast cancer overall; however, the risk was notably lower among African-American and Caucasian women with long-term use, according to a study by the University of Hawaii and University of Southern California.

The researchers' work is one of the first to explore the relationship between COX-2 inhibitors (aspirin and NSAIDs) and breast cancer in a multiethnic population. The National Cancer Institute is currently studying COX-2 drugs (short for cyclooxygenease-2) for its effect on breast cancer. The COX-2 enzyme is activated in response to inflammation and precancerous and cancerous tissues, and its inhibition has been associated with significant reduction in breast cancer tissue. A few large research studies have also shown a reduction in risk of breast cancer among NSAID users.

While COX-2 research has found a promising association with NSAIDs and cancer, Jasmeet Gill, Ph.D., postdoctoral fellow in the Department of Etiology, and her colleagues found no associations between aspirin and other NSAID (ibuprofen, naproxen, indomethacin, etc) use and breast cancer risk, even if the women's total NSAID use (aspirin plus other NSAIDs) was for 11 or more years. There were two exceptions: African-American women cut their breast cancer risk by more than half if they took NSAIDs other than aspirin for 6 or more years, and Caucasian women likewise cut their cancer risk by 30 percent.

"The COX-2 research and the NSAID studies led us to consider whether anti-inflammatory drugs might have different associations with breast cancer risk across ethnic groups," said Gill. "We are not sure why we didn't see a reduction in breast cancer incidence for aspirin users as other studies have shown, but we are intrigued by the reduced risk we observed among African-American and Caucasian women who used other NSAIDs. We believe more studies with detailed dosage information need to be conducted to resolve the role aspirin and NSAIDs play in the inhibition of breast cancer development." Gill cautioned that their study did not collect information on dose and frequency of aspirin or other NSAID use.

The researchers followed a cohort of 99,553 African-American, Caucasian, Japanese, native Hawaiian and Latina women from Hawaii and Los Angeles County between 1993 and 2002. When examining the risk of breast cancer from aspirin and other anti-inflammatory drugs, they found that body mass, tumor stage, or age had no consistent effect on the NSAID-cancer association.

Parity and risk of lung cancer

Women's reproductive behavior (having children or not) may increase their risk of lung cancer later in life, a study at the Harvard School of Public Health has found.

Jessica Paulus, a graduate student in epidemiology, and her colleagues studied data from 1,075 women with lung cancer and 867 cancer-free women who took part in a research study from 1992 to 2004 at the Massachusetts General Hospital in Boston. The researchers found that women who had any children (one or more) had nearly 40 percent less risk of lung cancer as compared to women without children. That risk of lung cancer also declined in a linear fashion with increasing numbers of children born.

"Patterns of lung cancer incidence suggest that women may be at a greater risk of lung cancer as compared to men," said Paulus. "Given the role of estrogen as a risk factor in other cancers, and the relationship between number of births and estrogen levels in the body, we hypothesized that having children may be associated with lung cancer risk in women."

While the researchers found a linear relationship between lung cancer and number of children, having one child did not significantly decrease the cancer risk compared to women who never had given birth. Having two children reduced the risk of cancer by 20 percent, and having three or more children reduced that risk by 40 percent.

The protective effect of childbearing was strongest -- but not significant statistically -- in women who had never smoked as compared to current and former smokers. Also, the protective effect of childbearing on lung cancer risk was limited to cases of average age of onset, and was not observed in women diagnosed with lung cancer before age 55 years.

"Our study supports the idea of an inverse relationship between having children and the risk of lung cancer among women," Paulus said. "While smoking behavior remains the strongest risk factor for lung cancer in women, our work indicates a need to further examine the role played by reproductive factors in lung cancer."

Risk factors for renal cell carcinoma in the multiethnic cohort study

Moderate alcohol consumption may lower the risk of renal cell carcinoma, but only in men, while exercise may also reduce risk, but only in women.

Renal cell carcinoma, the most common malignant kidney tumor, has no known cause but has been associated with a number of risk factors. A study by the universities of Southern California and Hawaii found that risks of renal cell carcinoma rise sharply with being overweight, smoking or hypertension, and decrease with physical activity and moderate alcohol consumption.

Wendy Setiawan, Ph.D., assistant professor of preventive medicine at USC, and her colleagues studied data from 167,200 ethnically diverse Americans who had participated in a study from 1993 to 1996. During an eight-year follow-up period, the researchers found 246 men and 129 women who were diagnosed with renal cell carcinoma.

"By examining the association between body size, physical activity, smoking, alcohol consumption and medical conditions, we discovered that body mass index (BMI) increases risk, smoking and hypertension had independently higher risks of cancer, while physical activity and drinking appeared to reduce the risks," Setiawan said. "While smoking has long been associated with the cancer, some of the other risk factors are newly found associations and merit further study in preventing the disease."

The risk of renal cell cancer increased incrementally with every rising unit of BMI (measured as weight divided by height squared), especially among women. Being obese with a BMI over 30 posed a 1.5 times higher risk of cancer for men, and more than 2 and a third times higher risk for women. Hypertension increased the risk by one-and-a-half times for men and more than one-and-two-third times for women. Cigarette smoking, long considered a risk factor, was confirmed by the study.

Increased alcohol consumption, however, reduced the risk by about one-third, but only among men. In addition, physical activity reduced risk only among women.

Renal cell carcinoma, marked by the growth of malignant tumors in the lining of the kidney's tubules (which carry urine and other wastes from the blood into the bladder), constitutes 90 percent of all malignant kidney cancers. About 38,900 Americans are diagnosed with the disease each year; of that, about 12,800 die. Its occurrence is increasing by about 1.5 percent each year. The cause of the disease, as well as of its increased occurrence, remains a mystery.

# # # #

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 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:
Warren Froelich
(215) 440-9300, ext. 198
froelich@aacr.org
In Boston (11/12-11/15):
(617) 954-2756

Diet Can Provide Protection against Development of Certain Cancers, New Studies Show

registration@aacr.org () — Tue, 14 Nov 2006 12:00:00 GMT

BOSTON - With cancer, researchers don't believe "you are what you eat" -- that disease is always a direct result of what is, or what isn't, on your dinner plate. But studies into the association between diet and cancer show that food can have an impact in preventing cancer, or in reducing the aggressiveness of the disease. At the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting, investigators have found that eating fish regularly as an adult, or soy as a young girl, or using a specific vitamin if you are a smoker, can help to protect against development of certain cancers. Another study found that blood cholesterol, some of which comes from eating animal fats, doesn't control whether a man develops prostate cancer, but lower levels of these lipids may help protect against aggressive forms of the disease. The researchers say these studies provide some of the strongest links found to date between diet and cancer.

Childhood soy intake and breast cancer risk in Asian-American women

In a novel study of Asian-American women, a team of researchers led by National Cancer Institute (NCI) investigators has found that consuming soy during childhood, adolescence and adult life were each associated with a decreased risk of breast cancer, but that the strongest and most consistent effect was seen for childhood intake.

They found that women who ate the most soy-based foods (such as tofu, miso, natto) during ages 5-11 reduced their risk of developing breast cancer by 58 percent, compared to women who ate the least amount. The corresponding reductions for adolescent and adult intake were about 25 percent.

"Childhood soy intake was significantly associated with reduced breast cancer risk in our study, suggesting that the timing of soy intake may be especially critical," said the study's lead investigator, Larissa Korde, M.D., MPH, a staff clinician at the NCI's Clinical Genetics Branch, in the Division of Cancer Epidemiology and Prevention. Korde worked in collaboration with epidemiologists at the University of Hawaii, the Northern California Cancer Center, and the University of Southern California.

The underlying mechanism is not known. However, Korde said that one hypothesis for the decreased risk associated with childhood intake is that soy isoflavones have estrogenic effects that cause changes in breast tissue, leading to decreased sensitivity to carcinogens. A similar protective effect has been found in studies of overweight girls, perhaps because fat tissue also secretes estrogens, she added.

"Hormonal exposures in adulthood, such as use of estrogen and progesterone replacement therapy, are established breast cancer risk factors. However, a growing body of evidence suggests that hormonally related exposures early in life may also modify susceptibility to breast cancer," Korde said.

Studies investigating adult soy intake and breast cancer risk have had mixed results, but the two studies that looked at adolescent consumption found that the risks of developing breast cancer later in life were cut in half. This study is the first to address the relationship between soy consumption during childhood and future risk of breast cancer.

As provocative as the findings are, the senior investigator on the study, Regina Ziegler, Ph.D, MPH, cautioned that it would be premature to recommend changes in childhood diet. "This is the first study to evaluate childhood soy intake and subsequent breast cancer risk, and this one result is not enough for a public health recommendation," she said. "The findings need to be replicated through additional research."

The researchers conducted a case-control study of women of Chinese, Japanese and Filipino descent who were living in the San Francisco Bay area, Los Angeles, or Oahu, Hawaii. Included were 597 Asian-American women with breast cancer and 966 women without the disease, who answered questions about their adult and adolescent diet and lifestyle. In addition, for a subset of 255 participants whose mothers were alive and living in the US, the mothers were asked about their daughter's early childhood exposures.

Soy intake was then divided into thirds, based on frequency of consumption, and by comparing the highest category to the lowest, the researchers found an inverse association between the risk of developing breast cancer and the amount of soy consumed. The childhood relationship held in all three races and all three study sites, and in women with and without a family history of breast cancer. Since the effects of childhood soy could not be explained by other measures of Asian lifestyle during childhood or adult life, researchers concluded that early soy intake might itself be protective.

A prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men

Men who ate fish five times a week or more had a 40 percent lower risk of developing colorectal cancer compared to men who ate fish less than once a week, according to a new analysis of data from 22,071 participants in the Physicians' Health Study (PHS).

The researchers say the reduction in colorectal cancer risk is substantial in comparison to other dietary components, and while they don't suggest that everyone starts eating fish daily simply because of these results, they say the health benefits of fish consumption have already been proven.

"We already know that eating fish can reduce the risk of sudden cardiac death, and this might provide another reason to add fish to your diet," said Megan Phillips, a doctoral student at the Harvard School of Public Health and the lead author of this study.

The researchers believe the health effects of fish consumption in relation to colorectal cancer may lie in their content of the n-3 fatty acids that can inhibit the cyclooxygenase-2 (COX-2) enzyme. This enzyme acts as a mediator of inflammatory responses thought to be associated with cancer development.

The PHS was designed as a randomized, double blind, placebo-controlled clinical trial to examine the effect of aspirin and beta-carotene supplements on development of cancer and cardiovascular disease, and the participants filled out a one-time food questionnaire 12 months after starting the study. In this analysis, investigators were also trying to determine if fish consumption had a different effect on men who received aspirin for five years compared to men who weren't randomized to use aspirin, which is also a COX-2 inhibitor. "We thought that maybe for men who received aspirin, it wouldn't matter whether they ate fish or not," Phillips said.

The researchers looked at four different categories of fish consumed - tuna fish, dark meat fish (salmon, sardines, bluefish, etc.), a general fish category, and shellfish including shrimp, lobster and scallops - and asked how many times the participants ate them on average during the previous year. They found almost 10 percent ate fish less than once a week, 31 percent ate it less than two times a week, 48 percent ate fish less than five times a week, and about 11 percent ate it five times or more a week. They then compared these figures with incidence of colorectal cancer that later developed in the men. (The average follow-up was 19.4 years).

They found that compared to men who ate the least amount of fish, the risk of developing colorectal cancer was 40 percent lower in men who ate the most fish, was 20 percent lower in men who ate fish 2-5 times a week, and 13 percent lower among participants who ate fish less than two times a week.

The relationship between fish consumption and colorectal cancer was similar for men randomized to aspirin and those who weren't, possibly because the researchers only had information on aspirin use during the first five years in the trial, and "it may take more years of aspirin use to see an effect," Phillips said.

While she said the results are promising, Phillips also noted that they are based on the assumptions that the pattern of fish consumption observed in the sole food questionnaire represented a diet that the men subsequently followed for many years.

In addition, men who consumed more fish may also have a healthier lifestyle perhaps including better cancer screening. Although this study controlled for some of these factors such as cigarette smoking, vigorous exercise, and multivitamin use, the investigators do not have information on colorectal endoscopies. Thus, these findings need additional confirmation through other prospective studies with more complete information and a definitive answer might require a randomized trial, said senior author Jing Ma, M.D., Ph.D., a researcher at the Brigham and Women's Hospital-based Channing Laboratory and associate professor of medicine at Harvard Medical School.

The relationship between dietary antioxidants and oxidative damage in smokers: evidence of effect modification by lifestyle and genetic factors

Vitamin E in the diet of male smokers appears to protect against oxidative damage that can lead to cancer development, according to researchers from Columbia University's Mailman School of Public Health working with investigators from the NYU School of Medicine.

They found that male smokers who had high plasma levels of vitamin E had lower levels of oxidative-DNA damage in their white blood cells. Oxidative DNA damage is a mechanism by which tobacco smoking can increase risk of cancer. In addition, the protective effect of vitamin E was greatest among the men with a beneficial form of a common "detoxifying" gene, GSTM1. The investigators did not find a similar effect of vitamin E in women.

"There was a dose-response relationship, in that the more vitamin E we found in the blood of the men, the less there was of this cancer-related biomarker," said the study's senior investigator, Frederica P. Perera, Dr.P.H., Professor in the Division of Environmental Health Sciences at the Columbia University School of Public Health.

"This suggests that while working toward the goal of quitting smoking, which is the very best way to prevent development of smoking-related cancers, it could be helpful to eat a diet rich in vitamin E," she said, and added, "we don't yet know why this relationship was not found in women, but a good diet is beneficial to health in many ways."

The most active form of vitamin E (known as α-tocopherol) is believed to be a strong antioxidant, capable of preventing oxidative chemical reactions that damage DNA. The vitamin is found in certain vegetable oils, nuts, whole grains, fish, green leafy vegetables and other foods. Studies that have examined the ability of vitamin E to protect against cancer have shown mixed results, however.

The present study is unusual, the researchers say, because it measured two different markers in white blood cells drawn from 280 participants - people who smoked at least 10 cigarettes a day. These markers were the amount of vitamin E in blood derived from food (those who used vitamins were excluded from this study) and the quantity of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a measure of oxidative damage to DNA.

The researchers found a protective effect of plasma α-tocopherol on oxidative damage among smokers, but only among men. They next looked at the interaction between vitamin E and GSTM1, a gene variant known to produce enzymes that efficiently detoxify carcinogens in tobacco smoke, and found a greater effect of the vitamin among men with this gene.

"We all want to know if vitamins help protect us against disease, and measuring their effects in the blood using markers of cellular damage is the most direct way to do that," said Perera. "But we have a lot of work ahead before we can fully understand the role of antioxidants in the chemoprevention of tobacco-related cancer."

Association between plasma cholesterol and prostate cancer

Prostate cancer patients who had lower levels of cholesterol in their blood had a significantly reduced chance of developing more aggressive forms of the disease, compared to patients with higher cholesterol readings.

These findings may help explain the earlier discovery, reported by the same team of researchers at the AACR annual meeting in 2005, that men who used statin drugs experienced half the risk of developing advanced prostate cancer.

"Statin drugs reduce cholesterol in the blood, but they also influence a number of different pathways," said the study's lead researcher, Elizabeth Platz, ScD, MPH, an associate professor in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. "This study suggests that the ability of statins to lower cholesterol may be important to prostate carcinogenesis, but we are continuing to examine other pathways with which statin drugs interact, such as reduction of inflammation."

The researchers looked at cholesterol levels first because cholesterol affects cell signaling and survival. Some scientists theorize that a large quantity of cholesterol in the blood could stimulate the survival of abnormal prostate cells.

They studied blood drawn from 698 men before they were diagnosed with prostate cancer and matched it to blood taken from 698 men who had not been diagnosed with the disease. All of the men participated in Harvard University's Health Professionals Follow-up Study, a group of 18,018 participants who provided a blood sample between 1993 and 1995.

They found that mean cholesterol levels did not differ between the men with prostate cancer and the control participants, suggesting that cholesterol was not involved in the initial development of prostate cancer, Platz said.

But when comparing men who had the lowest quartile of serum cholesterol to men who had the highest, they found that prostate cancer patients with lower cholesterol had the lowest risk of developing a more worrisome form of the disease. They specifically found that the risk of being diagnosed with high-grade or advanced cancer was reduced by 40 percent and 50 percent, respectively.

Platz says it is not clear at what levels serum cholesterol may stimulate the abnormal growth seen in cancer development. "The findings suggest either that high cholesterol may push existing prostate cancer to become aggressive, or, alternatively, very low levels of cholesterol may provide protection against development of an aggressive cancer," she said. "We just don't know which it is at this point."

She also said that because the findings come from an observational study, not a trial, it is impossible to conclude that men can lower their risk of developing an aggressive form of prostate cancer by reducing their intake of saturated fat, the type of fat that increases serum cholesterol, which some studies have linked to an increased risk of advanced prostate cancer.

"It is too soon to say that such measures would be specifically beneficial to lowering such a risk, but for good health in general, it is prudent to consume a diet that contains healthful fats that do not increase serum cholesterol," 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 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 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:
Warren Froelich
(215) 440-9300, ext. 198
froelich@aacr.org
In Boston (11/12-11/15):
(617) 954-2756

Plant-Derived Molecules, Genetic Manipulation Point to Future Chemoprevention Methods

registration@aacr.org () — Mon, 13 Nov 2006 12:00:00 GMT

BOSTON -- Scientists are using genetic studies and natural chemicals, such as plant-derived triterpenoids, to further our knowledge on how genetic and early molecular interactions can lead to cancer, and how those early interactions can be manipulated to stave off a variety of cancers. The latest studies with new and promising chemopreventive agents were presented at the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting today.

Trterpenoids and the rexinoid LG100268 prevent lung tumors induced by vinyl carbamate in strain A/J mice

New synthetic drugs called triterpenoids which owe their origins to plant molecules have demonstrated their effectiveness in slowing the growth of lung cancer tumors, a research team from Dartmouth University has found.

Following up on previous work showing strong links between inflammation and the development of cancer, Karen Liby, Ph.D., a postdoctoral fellow, and her colleagues found that the triterpenoid CDDO-MA, currently undergoing trails for leukemia and solid tumors (sponsored by Reata Pharmaceuticals), significantly reduced the number and sizes of tumors in mice. In addition, a chemically related drug developed by Ligand Pharmaceuticals called LG100268 was effective at preventing tumor growth.

"Lung cancer is the leading cause of cancer deaths in the United States," said Liby. "Since the mortality from this disease is significant, and prognoses are poor once a patient has been diagnosed, prevention may provide the only avenues to combat this particular cancer. We think this study shows a promising role for triterpenoids and the drug LG100268 in stopping lung tumor growth."

The scientists knew that the compounds had anti-inflammatory properties and that LG100268 in particular could stop certain types of breast cancer in animal models. The compounds inhibited inflammation in a number of ways: halting nitric oxide production, blocking cyclooxygenase and nitric oxide expression, curbing proliferation and inducing apoptosis in human lung cancer cells.

They tested CDDO-MA and LG100268 on mice for 20 weeks. CDDO-MA and 268 reduced the number of lung tumors to 9.1 in the group fed CDDO and to 7.4 in the 268-fed group, compared to 15.5 in the control group. These tumors were smaller, too: 43 percent of tumors in CDDO-fed mice and 28 percent of tumors in the 268-fed group were less than 0.5 mm in diameter, compared to only four percent in the control groups.

CDDO-ME and CDDO-EA, other synthetic forms of CDDO, also reduced tumors. After 15 weeks on a diet of the CDDO-ME triterpenoid, tumors numbered only 7.4, compared to 15.9 in the control mice. For mice on CDDO-EA, tumors were reduced to 7.8. No tumors in these groups were larger than 1 mm in diameter, while 20 percent of tumors in the control mice averaged more than this size. In fact, between 63 and 70 percent of tumors were less than 0.5 mm in diameter.

The research suggests the potential for these compounds in preventing lung cancer, and points to the need for clinical trials to test their effectiveness in humans.

The triterpenoid, CDDO-methyl ester, and the rexinoid, LG100268, synergize in the prevention of mammary tumors in a mouse model of estrogen receptor-negative breast cancer

Triterpenoids and the rexinoid experimental drug LG100268 were also effective in combination against breast cancer development more than either compound individually, the Dartmouth research team found.

Liby and her colleagues found that the synthetic triterpenoid CDDO-ME and the drug LG100268 eliminated tumors in mice that were fed the compounds. The work bolsters the potential for these drugs as a chemopreventive agent for an increasing range of cancers.

"We previously reported that the rexinoid LG100268 and another potential drug, Afzoxifene, which modulates the estrogen receptor, synergize in the prevention and treatment of certain mammary tumors in mice," said Liby. "This study takes our work further, establishing a relationship between CDDO-ME triterpenoids, which are also effective anti-inflammation and anti-cancer compounds, and LG100268."

The triterpenoid CDDO-ME had already been proven effective in inhibiting proliferation and inducing apoptosis (programmed cellular death, a process that's often disrupted in cancer) in breast cancer cells, and blocked the growth of breast cancer cells in mice. CDDO and its synthetic variant CDDO-ME are undergoing clinical trials for leukemia and solid tumors.

Beginning at 10 weeks of age, mice that were genetically altered to become susceptible to breast cancer were fed either a control diet, a dose of CDDO-ME, LG 100268, or a combination of the two. After 40 weeks, all the control mice developed tumors. However, only 12 percent of mice on the CDDO-ME diet and 29 percent of the mice fed with LG100268 developed tumors. Most significantly, no tumors were found in the group fed a combination of both drugs.

"The drugs that were fed in this experiment were apparently well tolerated, and the mice gained weight throughout the experiment," Liby said. "These studies indicate that CDDO-ME and LG100268, even as individual drugs, can delay tumor development in living organisms. But the combination of the triterpenoid and rexinoid compounds was particularly powerful. This synergy could hold the key to prevention of breast cancer and should be considered for future clinical trials."

Genetic reduction of circulating insulin-like growth factor (IGF)-1 inhibits azoxymethane-induced colon tumorigenesis in mice

Mice with a genetic alteration that reduced amounts of a key growth hormone had fewer carcinogen-induced tumors than mice with normal levels of the hormone, a research group from the National Cancer Institute (NCI), University of Texas-Austin and Mount Sinai School of Medicine found.

The research suggests that reducing levels of the growth hormone IGF-1 could prove to be a promising method for preventing colon cancer from developing. It is also the first known study to successfully develop a way to examine depleted IGF-1 function in living animals.

Susan Olivo-Marston, Ph.D., a postdoctoral fellow at the NCI, and her colleagues found that mice that lacked a gene that ultimately resulted in drastically reduced IGF-1 in the livers of mice had nearly half the number of tumors seen in mice with normal IGF-1 levels. Specifically, they found that mice with normal IGF-1 levels had an average of 13 colon tumors, but the IGF-deficient mice had only 7.2 tumors on average. In addition, the colon tumors in IGF-deficient mice were less likely to be found in the proximal colon; 25 percent of tumors were in the proximal colon of deficient mice, compared to 60 percent in the control mouse colons.

Since IGF-1--in addition to its role in controlling the maximal, final growth of a young adult animal--also inhibits programmed cell death and stimulates colon epithelial cells, the scientists tested IGF-deficient mice for these cancer-causing characteristics. In fact, deficient mice had a decrease in proliferation in colon cells and an increase in apoptosis.

The researchers were presented with a significant challenge, in that directly knocking out expression of IGF-1 in mice resulted in severe developmental abnormalities and very low survival rates. Therefore, the researchers found an existing type of mouse that lacked a gene called igf1 in the liver. These mice are IGF-1 deficient, but develop normally and have a 75 percent reduction in circulating levels of IGF-1.

"High levels of IGF-1 have been associated with significant increases in colon cancer risk" said Olivo-Marston. "Since IGF-1 inhibits apoptosis and stimulates colon epithelium proliferation, we hypothesized that reducing, if not eliminating, its function could prove an effective deterrent against colon cancer growth. This small pilot study will need more follow-ups to verify our findings that reductions in IGF-1 may prevent colon tumor formation."

Olivo-Marston's colleagues include Drs. Curt Harris and Jackie Lavigne at NCI, and Stephen Hursting at the University of Texas.

# # # #

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 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:
Warren Froelich
(215) 440-9300, ext. 198
froelich@aacr.org
In Boston (11/12-11/15):
(617) 954-2756

How Diet, Obesity and Even Gum Disease May Affect Immune System and Cancer

registration@aacr.org () — Mon, 13 Nov 2006 12:00:00 GMT

BOSTON - The immune system is fickle, and easily influenced by more than just viruses and bacteria. It can be swayed by the seemingly unexpected, such as by what we eat, for example, and affected by surprising sources. At the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting, scientists are taking a closer look at the link between increasingly common lifestyle factors, the immune system and cancer, with the ultimate goals of preventing and better understanding cancer development.

A Prospective Study of Periodontal Disease and Pancreatic Cancer

Can diseased gums increase the risk of pancreatic cancer? Epidemiologists at the Harvard School of Public Health in Boston think it could, at least according to the findings of a study analyzing 16 years of health data on more than 52,000 men.

Dominique Michaud, Sc.D., assistant professor of epidemiology in the Harvard School of Public Health in Boston, and colleagues at Dana-Farber Cancer Institute and the University of Puerto Rico wanted to know if inflammation, and specifically, systemic inflammation from periodontal disease, might be related to pancreatic cancer.

According to Michaud, several studies have linked inflammation and cancer, and researchers have found a high risk of developing pancreatic cancer among individuals with pancreatitis, or inflammation of the pancreas. But the ties between periodontal disease and cancer have been more tenuous.

Previous studies have shown associations between tooth loss and cancer, and pancreatic cancer as well. But the validity of such studies was questionable because of confounding factors, including smoking, which contributes to both periodontal disease and cancer. An association with periodontal disease and heart disease has also been examined, with systemic inflammation being a potential mechanism behind the connection. Periodontal disease results in chronic inflammation over many years, both in the mouth and potentially, systemically, as well.

The researchers analyzed the health records of a fairly homogenous group of about 52,000 highly educated, male health professionals between ages 40 and 75 who participated in the Health Professionals Follow-up Study, which was created in 1986 to look at lifestyle factors related to cancer and other chronic diseases. They continue to be followed at present through mailed questionnaires, with a greater than 95 percent follow-up rate, Michaud said.

The researchers recorded 216 cases of pancreatic cancer in the 16 years of follow-up between 1986 and 2002. Men who reported having periodontal disease had a 63 percent higher risk of developing pancreatic cancer compared to those who did not report periodontal disease, after the team adjusted for smoking, diabetes, age, physical activity and diet. Those men who never smoked fared even worse, with a two-fold increase in risk. Men who reported a history of periodontal disease and tooth loss in the last four years showed a more than a 2.5-fold increase in the risk of developing pancreatic cancer compared to those without periodontal disease and recent tooth loss.

In a secondary analysis, the team looked at tooth loss at both the beginning of the study (baseline) and during the follow-up period. While tooth loss at baseline was not associated with a risk of pancreatic cancer, those who lost teeth during follow up showed an increased, albeit lesser, risk for pancreatic cancer. Tooth loss among older individuals is likely due to periodontal disease, Michaud explained, whereas tooth loss at enrollment in the study is more likely to reflect teeth that were lost or removed because of cavities.

"The results confirm our hypothesis that pancreatic cancer is related to periodontal disease, not merely tooth loss," Michaud said.

Other potential mechanisms, she said, include the fact that those with periodontal disease have high amounts of bacteria in the mouth and in the gut, and also tend to have higher amounts of nitrosamines, which have been proposed to increase pancreatic cancer risk.

"The work might provide new insights in understanding the role of systemic inflammation on initiation or promotion of pancreatic cancer," she said. Smoking, she noted, is a risk factor that could be acting as a promoter by causing inflammation.

"Establishing whether periodontal disease increases the risk and understanding the mechanisms behind these associations are important because we know so little about pancreatic cancer."

Pancreatic cancer, the fourth-leading cause of cancer death in this country, takes some 30,000 lives a year.

Diet-Induced Obesity Impairs Both Innate and Adaptive Immune Responses

Obese mice experience a far lower immune response than do normal weight mice to a vaccine typically given to cancer patients, according to studies by National Cancer Institute immunologists.

The diminished immune activity not only may explain the connection between obesity and heightened cancer risk, it also suggests that obesity might reduce the effectiveness of common vaccines, such as flu and tetanus.

According to Connie Rogers, Ph.D., MPH, a research fellow at the Laboratory of Tumor Immunology and Biology at the National Cancer Institute (NCI) in Bethesda, several studies over the years have implicated obesity with diminishing immune function. In the early 1990s, studies showed low antibody levels after vaccination in those who had a high Body Mass Index, or BMI, which is a measure of body fatness.

"We hypothesized that perhaps there are global immune impairments that occur in the face of obesity, and in turn, maybe this is one of several mechanisms that might lead to, or mediate, the relationship between obesity and tumor risk," she said.

Rogers and co-workers at NCI and at the University of Texas compared the immune system function of lean, overweight and obese mice. They created lean mice by slightly restricting their diets and watching carbohydrates. Mice that were given unlimited access to food with a mildly fat content, about 10 percent versus the usual 5 percent to 7 percent fat in their diet, became overweight. Mice that were given unlimited access to a diet made up of about 60 percent in fat, similar to consuming a diet plentiful in fast-foods, became overweight to obese.

"The mice differed in body fat," Rogers noted, "and we wanted to tease out whether it was the weight or body fat that impaired immune function, and if there was a fat threshold in regard to immune function."

The researchers injected mice with a vaccine usually used for cancer patients and which targeted tumor antigens commonly seen in breast, prostate or colon cancers. By stimulating the immune system and measuring a specific response, they could compare the extent of obesity-induced immune function impairment in each animal body type.

"We needed to simulate the immune system and be able to measure a specific response," she said. The study also served "as a tool to probe the immune system and to shed some light on whether obesity might be impacting patients we see who come in for cancer vaccine treatment."

The scientists gave mice a primary vaccination and two booster vaccines to mimic as closely as possible the schedule used in patients. They examined both the broad-based or innate immune responses, and the adaptive immune responses, including T- and B-cell responses to vaccination. While adaptive immune responses require prior exposure to a foreign protein such as a virus or bacterium, innate immunity does not.

"Interestingly, it looks like both innate immune responses such as natural killer cell function and T-cell proliferation to broad-based stimuli were impaired, and importantly, their adaptive immune responses to the vaccine were impaired," Rogers said. The group found that the obese mice failed to develop appropriate antibody levels and "their ability to proliferate in response to the vaccine antigens was impaired." Both are important for generating an adequate immune response to a vaccine.

Neither the lean mice nor the moderately overweight mice showed similar immune system impairments in response to vaccination, suggesting that the response might be a "stepwise decrease" in adaptive immunity, Rogers said.

"I think we now know that this obesity-induced impairment is fairly widespread, and affects many components of the immune system," she said. "The clinical and public health importance of this is that there are probably some significant long-term consequences. We targeted many components of the immune system, and several, such as general response to infection and tumor response to vaccine, for example, could be affected by this obesity-induced impairment in immunity."

"In the long term, we're considering the usual cancer patient who is in his sixties and probably overweight," Rogers said. "But a basic biological question and one with public health significance is that of general immune health of overweight or obese people. That has an impact on long-term health."

Rogers and her team have several questions to explore. "Now that we know about obesity-induced impairments in immune function, we want to know whether these can be reversed by interventions, such as diet and exercise," she said. "Is a person permanently immunologically impaired, or can losing weight, body fat or both, reverse the effects, or is some other mechanism involved?" Such studies involving diet and exercise currently are underway in animals.

A 23-Year Survival Analysis of Prediagnostic BMI and Risk of Lethal Prostate Cancer

A team of Harvard scientists has peered into 23 years of health data on more than 22,000 physicians and concluded that men who are overweight or obese years before being diagnosed with prostate cancer are more likely to die of the disease than those who are of normal weight.

While no studies have definitively shown that obesity and/or higher Body Mass Index, or BMI, which measures body fat, increases the risk of developing prostate cancer, these studies showed that obese men at the time of diagnosis were more likely to have a cancer recurrence.

But according to Jing Ma, M.D., Ph.D., a researcher at the Brigham and Women's Hospital-based Channing Laboratory and associate professor of medicine at Harvard Medical School, few studies have focused on obesity and the risk of dying from prostate cancer.

In fact, she said, there is "considerable debate in the urology and cancer fields regarding whether rising PSA (Prostate Specific Antigen) is a good indicator for whether people will eventually die from prostate cancer or not."

Ma and her co-workers at Brigham and Women's Hospital and at the Harvard School of Public Health examined 23 years of data from the Physician's Health Study, which began in 1982 as a randomized, double-blind trial of aspirin and beta-carotene. More than 22,000 U.S. male physicians were recruited for the trial to study the role of aspirin and beta-carotene in preventing heart disease and cancer.

About 15,000 men provided blood samples at enrollment, along with information on their body weight and height, and their BMI was calculated. Approximately 99 percent of the original participants were tracked through questionnaires for 23 years, including cause of death.

By the end of 2005, 2,367 men had developed prostate cancer, while 265 died of the disease. They found that 39 percent of the participants were overweight and 3.4 percent were obese at the beginning of the study, and that higher BMI was positively associated with the risk of dying from prostate cancer. They also showed that the risk of dying from prostate cancer increased 8 percent for each point increase in BMI.

A person with a BMI of between 25 and 29.9 is considered overweight, whereas someone with a BMI of 30-plus is called obese. The physicians were in relatively good shape compared to the U.S. population in general. U.S. males between 50 and 69 are approximately 40 percent overweight and more than 30 percent are obese.

"It was surprising since it is a moderate association and the BMI was measured in 1982 and was on average eight to 10 years before developing prostate cancer," Ma said. "The beauty of the study is that we could factor out smoking at baseline, and tumor grade and stage didn't affect the trend."

"Some people might think that what they do today has little to do with cancer risk, especially for prostate cancer," Ma said, "and some individuals probably wouldn't believe that obesity has anything to do with prostate cancer. But we have found that if a man develops prostate cancer, being obese could put him at a higher risk of dying from the cancer. There is something many men can do about that."

She and her co-workers are exploring the underlying mechanisms that link being overweight and/or obese to prostate cancer progression. A better understanding of the risk factors that influence the disease's progression, said Ma, is imperative.

Prostate cancer is the most common type of cancer found in American men, other than skin cancer, and the third leading cause of cancer death in men. The American Cancer Society estimates that there will be about 234,460 new cases of prostate cancer in the United States in 2006, with approximately 27,350 deaths from the 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 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 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:
Warren Froelich
(215) 440-9300, ext. 198
froelich@aacr.org
In Boston (11/12-11/15):
(617) 954-2756

Genes Offer Researchers a “Crystal Ball” to Help Them Prevent, Diagnose, and Treat Cancer

registration@aacr.org () — Sun, 12 Nov 2006 12:00:00 GMT

BOSTON - The science of cancer prevention has advanced to the point where researchers now say they can detect "cancer genes" in the breath of smokers, and can test the presence of two proteins in men they say will predict development of prostate cancer a decade in advance. All of these novel findings need much more examination, of course, but scientists at the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting, say these examples illustrate how it is becoming increasingly possible to use genes and their protein products to help predict and diagnose cancer, as well as choose therapy that offers the most potential for a good result. These researchers will also discuss a test that can pick out patients who have pancreatic cancer - an advance that offers hope the disease can be treated at earlier stages than it is now - and how several unique genes can predict which prostate cancer or lung cancer patients will develop aggressive tumors that need additional treatment. Cancer is a disease of genes, they say, so genes can be employed as a crystal ball to thwart the disease.

Lung carcinogenesis tracked by DNA methylation mapping in exhaled breath

For the first time, researchers have demonstrated that it is possible to detect DNA methylation in the breath of smokers and lung cancer patients, suggesting that, in theory, it may be possible to use this technique to identify people who have undiagnosed lung cancer or are at high risk of developing the disease.

Investigators at the Wadsworth Center, the public health laboratory of the New York State Department of Health, have been able to develop an assay that simultaneously detects the presence of methylation in six tumor suppressor genes - a process by which a gene is chemically silenced. The assay examines the promoter region of a gene, where certain cytosine nucleotide bases may be methylated, preventing the gene from being expressed.

The seven participants tested so far breathe for ten minutes into a commercially available handheld device, which cools the air, forming a condensed vapor, to which the methylation assay is applied. Investigators found it could detect the presence of the methylated form in all six tumor suppressor genes. For RASSF1A, the test was negative in non-smokers, and positive in both current and ex-smokers. For DAPK, methylation was more variable, given smoking status. The four other tested genes (p16, MGMT, PAX5B,CDH1) known to be methylated in various stages of lung cancer development, were minimally or not methylated, in this pilot study of predominantly cancer-free smokers.

"Dr. Weiguo Han and I have shown that this approach is technically feasible, and if further research demonstrates the assay can measure DNA in such a way that it diagnoses or predicts lung cancer, this could be important for non-invasive lung cancer testing," said the study's lead author, Simon D. Spivack, M.D., M.P.H., a research physician at the Wadsworth Center, and a specialist in lung diseases. "But we are a long way from that point." Han, a post-doctoral fellow in Spivacks' laboratory and the study's first author, will be presenting the findings.

Spivack said his study was only the third to date that proved DNA could be tested in condensed breath - German researchers reported the first such result in 2003, followed by an Italian group in 2005 - and the first to find methylation-silenced tumor suppressor genes in the breath of patients at risk or harboring lung cancer.

"The concept of testing exhaled breath is not new - that's what breathalyzers do when they measure small volatile molecules such as alcohol, as well as inflammation molecules that are currently being assayed to test the activity of asthma and other lung diseases," said Spivack. "But what is rather remarkable here is that DNA can be tested in the air that comes from the lungs and airways, and that it might be possible to use this in diagnosis of lung cancer in particular, and gene-dysregulation disorders of the lung, in general."

The DNA is believed to be released when cells turn over, or are damaged, in the lungs and airways, he said. "Although it is not possible to say at this point the precise anatomic origin of the airway-derived DNA being tested, it may be that different patterns of gene methylation will themselves actually map the origin of this DNA to particular regions of the airway," Spivack said.

"Our goal is early detection of lung cancer and risk stratification," he said. "If all we can do is confirm that a smoker is smoking, or that a lung cancer patient has cancer, then this test will be meaningless. But we now know it is technically feasible to measure DNA methylation in breath."

Multiplexed serum markers screening for detection of pancreatic cancer

A panel of 10 blood biomarkers performed almost perfectly in picking out people who had pancreatic cancer from those who didn't, according to researchers at the University of Pittsburgh. The advance raises hopes that a test can be developed to screen for the aggressive cancer in time to treat it, they say.

"Early detection of pancreatic cancer is crucial to survival, but there has been no way to diagnose it early before symptoms occur," said the lead investigator, Anna E. Lokshin, Ph.D., an associate professor of medicine and pathology at the University of Pittsburgh School of Medicine. "This assay represents a new way to screen for disease that appears to be applicable to pancreatic cancer, and potentially, to other cancer types."

The assay contains the largest panel of blood-based biomarkers to be examined simultaneously in pancreatic cancer. It consists of proteins known to be secreted by pancreatic tumors as well as proteins that represent the body's response to that tumor growth, Lokshin said.

"Tumors are located in the context of certain tissues, and those tissues react in their own individual ways to the cancer," she said. "For example, tissue-specific proteins try to fight the cancer, and each tumor type grows blood vessels in tissue uniquely, so we believe the body responds differently to each kind of cancer."

The researchers initially evaluated a panel of 44 protein biomarkers, including cytokines, chemokines, adhesion molecules and hormones, and used blood from 100 pancreatic cancer patients and a control group of 400 healthy people to find those associated with the cancer. They used a microbead array, which can sample up to 100 different proteins simultaneously, and found 10 biomarkers that offered the highest diagnostic power, Lokshin said. Two of those biomarkers are CA125, which can detect a number of cancers but which is not very specific, and CA19-9, which has been known to correlate weakly with pancreatic cancer.

They found that this panel of markers correctly identified pancreatic cancers 97 percent of the time, with a sensitivity of 95 percent (meaning it could correctly identify cancerous lesions) and with a 98 percent specificity (the ability to detect truly negative cases).

The researchers are continuing to study, validate, and perfect the assay, and test its ability to identify pancreatic cancer at early, treatable stages. Although pancreatic cancer is relatively rare, survival is poor compared to most other forms of cancer - it is the fourth leading cause of cancer-related deaths in males and the fifth-leading cause of cancer-related deaths in females.

A diagnostic screen for pancreatic cancer would likely first be used in smokers, because use of tobacco is a known risk factor for developing pancreatic cancer, Lokshin said.

The researchers also are developing similar assays for ovarian, breast, lung, endometrial, head and neck, and esophageal cancers. "So far, every panel is different for each cancer to the point where we can say with greater than 97 percent certainty which cancer it is," she said.

"Surprisingly, although in theory body response could be similar for several cancers, in practice it is very different."

TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion

The presence of a gene fusion in prostate tumors is significantly associated with aggressive cancer, metastatic spread, and an increased probability of death, a team of researchers is reporting. They say that the new gene, formed by the fusion of TMPRSS2 and ERG, may serve as a biomarker to separate patients who might benefit from radical prostate cancer therapy from those who potentially need little, if any, treatment.

"We believe this gene has the potential to be used as a diagnostic and prognostic test, which could offer thousands of patients peace of mind and spare them from unnecessary surgery and therapy," said the study's lead author, Sven Perner, M.D., a postdoctoral fellow in the Department of Pathology at Harvard University's Brigham and Women's Hospital in Boston. He worked with researchers from the Universities of California and Michigan, Johns Hopkins University and McGill University in Montreal.

Perner and his colleagues reported the discovery of the fused gene last year and they now say that TMPRSS2-ERG occurs in about 50 percent of prostate cancers - making it the most common genetic aberration in human cancer, and the first one found in a common solid cancer. Fused genes and chromosomal rearrangements have been found in several blood cancers, such as chronic myelogenous leukemia (CML) and in soft tissue tumors, such as Ewing's sarcoma, but these diseases are rare compared to prostate cancer, which is one of the leading cancers among American men.

In this study, the researchers sought to learn whether TMPRSS2-ERG is associated with a particular prostate cancer stage, and how it might be contributing to development of the cancer. They gathered 406 prostate tissue samples, representing a range of benign, precursor, and malignant prostate lesions, and used a FISH analysis to look for TMPRSS2-ERG. They didn't find any evidence of the fused gene in non-cancerous samples, but found it was present in 48.5 percent of localized prostate cancer tumors, 30 percent of hormone-naïve metastases, and in 33 percent of hormone refractory metastasis, as well as in about 20 percent of prostatic intraepithelial neoplasias, a lesion believed to be precursor of invasive prostate cancer.

The investigators also discovered that the gene fusion could occur in two different ways. The genes, TMPRSS2, which is regulated by the male sex-hormone androgen, and ERG, which is a potential oncogene, are located close to one another on chromosome 21. When fused, TMPRSS2 drives over-expression of the ERG gene. According to Perner, fusion can occur when the piece of DNA separating the genes breaks off and the genes merge (a process described as "fusion through deletion"), or if parts of each gene break off and switch positions ("translocation").

They found that TMPRSS2-ERG fusion through deletion was more common in the tumor samples as compared to TMPRSS2-ERG fusion through translocation. More recent work has found a significant association between TMPRSS2-ERG fusion and death from prostate cancer, although the researchers have not yet been able to determine which fusion form predicted the highest risk of death.

Perner says investigators are hoping to find a small molecule to inhibit the TMPRSS2-ERG fusion protein in the same way that the drug Gleevec has revolutionized care of CML.

Prediagnostic interleukin-6, C-reactive protein and prostate cancer incidence and mortality

Increased levels of two markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), are significantly associated with prostate cancer incidence and mortality almost a decade prior to diagnosis, say researchers at the Harvard School of Public Health.

They also found that elevated CRP in these men was associated with a two-fold increased risk of developing fatal prostate cancer, compared to men with the lowest levels of the protein.

"The results of this study provide further evidence that inflammation is involved in development and progression of prostate cancer," said the study's lead author, Jennifer Rider Stark, a graduate student in epidemiology.

Stark said that IL-6 and CRP were more strongly associated with prostate cancer risk and death from prostate cancer in normal weight men. Because IL-6 is secreted from adipose (fat) tissue, levels of the cytokine are naturally higher in overweight or obese men. "It is possible that high levels of IL-6 and CRP in men with a healthy body weight may be more indicative of a pro-inflammatory environment in the prostate," she said.

Some studies have already shown that high levels of IL-6 and CRP can be associated with a poor prognosis in prostate cancer patients, but this is one of only a few studies to examine whether these markers can predict risk before symptoms develop and cancer is diagnosed.

The findings come from a prospective study nested within the Physician's Health Study, and included 516 men who later developed prostate cancer and 516 matched controls who did not. The researchers examined blood taken from each participant early in the study - a median of 9.4 years before prostate cancer was diagnosed in the cases. Levels of IL-6 and CRP were compared among men who did and did not go on to develop cancer. Long-term follow-up of the cases also allowed the researchers to assess the effect of these markers on prostate cancer mortality.

They found that high levels of CRP in the blood was associated with a higher incidence of prostate cancer development among all patients and associated with a two-fold increased risk of developing lethal prostate cancer. IL-6 levels were not associated with prostate cancer risk overall. But when they separated out men by body mass index, those who had a healthy weight and high IL-6 in their blood had a 40 percent higher risk of developing prostate cancer.

Researchers suspect that abnormal amounts of IL-6 and CRP are markers of biological processes involved in development of a number of diseases, including cancer. IL-6 is secreted by immune cells in response to infection or trauma, and it, in turn, stimulates synthesis of CRP in the liver, which is believed to play a role in response to infections and cellular damage control. CRP has been found to be a marker of cardiovascular disease, diabetes and colon cancer, but its use as a cardiology screening test has been controversial.

Stark noted that the predictive power of these two markers for determining prostate cancer risk and mortality needs to be confirmed in other prospective studies. She added, "Understanding the role of inflammation in prostate cancer is important because inflammatory pathways could potentially be targeted for prevention and treatment."

Characteristics of long-term lung cancer survivors

In preliminary findings from an ongoing study, researchers at Mayo Clinic have identified four different factors they say predicts long-term survival in patients diagnosed with lung cancer, and one of the strongest is inheritance of a gene variant, GSTM1 positive, which is more efficient than another allele type of the GSTM1 gene at detoxifying carcinogens.

They found that patients with a null type at this gene were four times more likely to die within two years as were matched patients who had the positive variant.

The researchers also found that patients who had surgery, who were active, and whose cancer did not come back or progress were much more likely to survive five years or longer.

"Outcome varies among lung cancer patients, even within groups that have the same stage at the time of diagnosis, and so it is difficult to know how aggressively to treat and provide follow-up care for individual patients," said the study's lead investigator, Ping Yang, M.D., Ph.D., a clinical and genetic epidemiologist at Mayo Clinic.

"In order to enhance both survival and quality of life, we are trying to establish a model that will identify patients who would benefit from additional clinical intervention, and the data we have accumulated to date could be enormously helpful," she said.

To derive these predictive factors, the researchers aim to compare 400 lung-cancer patients treated at Mayo Clinic and who have survived five or more years, with 400 patients who lived less than two years after treatment. The researchers match the groups by age at diagnosis, gender, tumor cell type, cancer stage and the number of primary lung cancers, and they examine blood samples and follow the progress of the patients' disease as well as their quality of life.

In an interim analysis of data on 150 patients in each group, the researchers specifically found that patients who experienced any progression or recurrence of their cancer were almost three times more likely to die within two years, compared to patients of the same cancer stage whose disease did not progress or return.

They also concluded that lung cancer patients who had surgery were three times as likely to have longer survival as matched patients who did not have surgery. "This can be very useful information for patients who are undecided about whether they should risk having surgery," she said.

Patients who reported being "unable to do work or could only do light work" were at a 2.7-5.8 fold higher probability of dying within two years than were patients who were active, the researchers also discovered. "The clinical care of these patients is a long- term process," Yang said. "If, through follow-up and monitoring, we find a patient is physically inactive, we may recommend exercise and rehabilitation as appropriate to keep them stronger."

Knowing the contribution of inheriting a GSTM1 gene form to outcome is also important, she said. "If our model tells us that a patient's cancer has a higher chance of recurring or progressing because of innate genetics in metabolism, we can watch them more closely, and consider treating them aggressively and promoting preventive measures," Yang said.

The GSTM1 gene is just one of many candidate genes the investigators are studying in these 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 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 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:
Warren Froelich
(215) 440-9300, ext. 198
froelich@aacr.org
In Boston (11/12-11/15):
(617) 954-2756

What Does the Public Really Know about HPV?

registration@aacr.org () — Sun, 12 Nov 2006 12:00:00 GMT

Researchers Gauge Women's Understanding of the Link to Cancer and Response to the New Vaccine

BOSTON - Human papillomaviruses (HPV) are the most common sexually transmitted infections in the United States, and certain "high risk" types have been shown to cause cervical cancer. Despite recent advances in the detection and prevention of HPV, the link between the virus and cervical cancer is not well known to the public. In June 2006, the Food and Drug Administration (FDA) approved the first vaccine to prevent infection of two high risk types of HPV, and two types that cause genital warts. The Advisory Committee on Immunization Practices (ACIP) recommended it for females 9 to 26 years of age.

Two studies presented today at the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting in Boston assess the public's understanding of HPV and whether discussion of the vaccine by the media and public has influenced the decision to vaccinate among women at risk.

What Do U.S. Women Know About Human Papillomavirus (HPV) and Cervical Cancer?

Many women with HPV show no symptoms of the virus, and infections often clear without need for treatment. Because of this, many women do not have the opportunity to speak with their physicians about HPV and therefore may not learn that some HPV infections are persistent and can develop into cervical cancer.

The National Cancer Institute (NCI) created the Health Information National Trends Survey (HINTS) to monitor health communications about cancer. In 2005, one high-priority research aim was to assess, for the first time, the awareness and knowledge of HPV in a nationally representative sample of women.

To identify factors associated with U.S. women's awareness of HPV and its link to cervical cancer, researchers from NCI analyzed cross-sectional data collected from more than 3,000 women ages 18 to 75 who responded to HINTS.

Researchers found that:

Only 40 percent had ever heard about HPV;

Among them, less than half were aware of the virus' connection to cervical cancer;

64 percent knew that HPV could be sexually transmitted, and 79 percent knew it could cause abnormal Pap smears.

The public needs education about HPV and cervical cancer in order to make appropriate, evidence-based health care choices among existing prevention strategies, including the Pap test, HPV DNA test, and HPV vaccine, researchers concluded.

"Individuals are constantly being presented with new health care research that updates previous knowledge, might conflict with prior knowledge, or provides entirely new options for diagnosis and treatment," said Jasmin A. Tiro, Ph.D., MPH, in the Division of Cancer Control and Population Sciences, NCI, Bethesda, Md. "With limited awareness about HPV among women in this country, there is a need for clear, consistent information about HPV transmission, prevention, detection and the link to cervical cancer. We expect that media coverage over the past year and direct-to-consumer marketing efforts by the makers of the HPV DNA test and the HPV vaccine will increase awareness, and NCI is conducting studies to monitor this possible increase. We plan to track the diffusion of knowledge to make sure that all women have accurate knowledge about HPV and how to prevent cervical cancer."

The Effects of Information Framing on Intentions to Vaccinate Against HPV

The success of the HPV vaccine depends largely on the public's willingness to accept vaccination. Because of the potentially controversial nature of the vaccine, researchers at the University of Pennsylvania's EPIC Center of Excellence in Cancer Communication Research assessed how its portrayal in the media would affect attitudes toward vaccination among women.

The study was a part of the Annenberg National Health Communication Survey, a monthly barometer of the public's health communication practices and needs. The survey is jointly funded by the National Cancer Institute, the Annenberg School for Communication and the Sunnylands Trust at Annenberg. It was fielded in June, 2006, roughly coinciding with FDA approval of the vaccine.

A nationally representative sample of U.S. adults over 18 was randomly assigned to read one of three paragraphs about the vaccine, each emphasizing a different point of view: the vaccine protects against cervical cancer; the vaccine protects against cervical cancer and sexually transmitted infections; or, the vaccine protects against cervical cancer, sexually transmitted infections and may or may not lead to increased sexual promiscuity among those vaccinated. The survey was then given to gauge intentions toward vaccination. It was completed by 635 adults, 49 percent of whom were women.

Researchers found:

More than half of respondents (56 percent) had heard of HPV and reported that they had seen or heard news or ads about HPV in the past week;

Although 42 percent of respondents had heard about a vaccine for HPV, 80 percent indicated never having talked to a health care provider about the virus.

How the vaccine was presented greatly affected women's intentions to vaccinate. When women read that the vaccine protects only against cervical cancer, 63 percent indicated they were "very likely" or "somewhat likely" to get vaccinated, compared to 43 percent of women who read that the vaccine protects against cervical cancer and a sexually transmitted infection.

"Despite high levels of exposure to and awareness of the newly approved HPV vaccine, intentions to vaccinate are mixed," said Amy Leader, MPH, Research Director, EPIC Center of Excellence in Cancer Communication Research. "Trends indicate that intentions are highest when the vaccine is framed to solely prevent cervical cancer and lowest when the vaccine is framed to prevent both cervical cancer and a sexually transmitted infection, or STI, indicating that people may feel the need for an STI vaccine is unnecessary."

Participants were also asked about their intentions to vaccinate if they had to pay for the vaccine or if the vaccine were provided at little or no cost. Although the majority reported having some form of health insurance coverage, intentions to vaccinate one's self or a daughter were substantially higher when the vaccine was available at little or no cost. For example, 54 percent of parents indicated that they were "very likely" or "somewhat likely" to want the vaccine for their daughter if it were provided at little or no cost, compared to 38 percent of parents who would consider the vaccine for their daughter if it would cost their 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 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 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:
Warren Froelich
(215) 440-9300, ext. 198
froelich@aacr.org
In Boston (11/12-11/15):
(617) 954-2756

Novel Vaccine Shows Promise against Early Stage Breast Cancer

registration@aacr.org () — Sun, 12 Nov 2006 12:00:00 GMT

BOSTON − A diagnosis of breast cancer has taken on a new meaning in the past 10 years, as research has produced a host of new therapies and detection techniques, significantly improving long-term survival for women who have been fighting the disease. To build on these successes, researchers are now harnessing what they have learned about treating breast cancer and applying it to possible methods of prevention to reduce the total incidence of the disease. One study presented today at the American Association for Cancer Research’s Frontiers in Cancer Prevention Research meeting in Boston looks at a specific target in the fight against breast cancer and evaluates a potential vaccine that is yielding promising results for women who are at high-risk for the disease.

Targeted immunoediting of critical pathways responsible for breast cancer development: treatment of early breast cancer using HER-2/neu pulsed dendritic cells

Multiple genetic targets have been discovered that may help fight breast cancer, including BRCA, estrogen receptors, and HER-2/neu, all of which have been known to predict the severity of disease, recurrence and overall survival. Developing novel therapies that target these specific genetic variances may be extremely beneficial in preventing breast cancer for many women.

In this study, researchers investigated a potential vaccine that targets HER-2/neu over-expression in early stage breast cancer, known as DCIS (ductal carcinomas in situ, or early stage cancer formation in the breast’s milk ducts). It is estimated at 50-60 percent of DCIS is directly related to HER-2/neu over-expression.

Patients with HER-2/neu overexpression were given a therapy of dendritic cells (DC, which work with the B- and T-cells to trigger immune responses) that were treated with HER-2/neu to evoke an immune response. The participants received four weekly vaccinations into normal lymph nodes in their groins and were evaluated both pre- and post-vaccination for immune response, level of HER-2/neu expression, and cell infiltrates.

The researchers found that most patients responded well to the vaccination. Nearly all patients (11 of 12) exhibited an initial immune response (shown by the presence of anti-HER-2/neu specific CD4+ T cells), and many of the patients developed protein antibodies to fight the HER-2/neu cells. Patients began to build up reserves of white blood cells following treatment and seemed to show long-term immune responses to HER-2/neu as a result of the therapy. Of the 12 study participants, six showed markedly reduced levels of HER-2/neu expression after the vaccination, and as a result, the investigators also noted an improvement in their severity of their disease.

“The results demonstrate for the first time that this DC vaccination may have significant clinical activity against certain types of breast cancer,” said Brian J. Czerniecki, M.D., of the University of Pennsylvania, and lead author of the study. “We are confident that targeted treatment with this vaccine may effectively fight not only DCIS, but may extend to prevention of breast cancer entirely.”

According to the American Cancer Society, approximately 200,000 women will be diagnosed with breast cancer in the U.S. in 2006, though thanks to new options for patients, about 20 percent, or 40,000 patients will die. Even with improved therapies, the chance of a woman having breast cancer at some time in her life is still about one in eight.

# # #

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 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:
Warren Froelich
215-440-9300 ext. 198
froelich@aacr.org
In Boston (11/12-11/15):
(617) 954-2756

First report that apoptotic and anti-angiogenic therapies work better together than alone

registration@aacr.org () — Fri, 10 Nov 2006 12:00:00 GMT

Prague, Czech Republic: American researchers have found that giving a combination of imantanib (Glivec¹) and a drug that induces cell death (apoptosis) was better at inhibiting the growth of Ewing's sarcoma in mice than either therapy on its own. Imantanib works by preventing the creation of new blood vessels to supply the growing tumour (antiangiogenesis) and the researchers believe that this is the first report of synergy between apoptosis and antiangiogenic therapy in pre-clinical work.

Professor Andrea Hayes-Jordan reported to the EORTC-NCI-AACR²Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Friday 10 November) that treating sarcoma cells with imantanib inhibited a growth factor called PDGFR-beta. This had the effect of increasing the sensitivity of the cells to a drug called tumour necrosis factor-related apoptosis-inducing ligand (TRAIL).

Prof. Hayes-Jordan, assistant professor of surgery and pediatrics at The University of Texas M. D. Anderson Cancer Center, Houston, USA, said: "When I treated the tumour cells with imantanib, the anti-angiogenic drug, the receptors for TRAIL, the apoptotic drug, increased, thus increasing the efficacy of TRAIL. This was supported by the mouse studies, which showed increased inhibition of pulmonary metastases and primary tumour growth when both were used simultaneously. These findings are important because, if it proves to be effective in humans, it would be well tolerated and have significantly fewer side effects than traditional cytotoxic therapy. Also, at present, we have no effective chemotherapy for pulmonary metastases - the only effective treatment is surgery - so this would give us another option." Prof. Hayes-Jordan hopes to investigate the dual therapy in humans in a clinical trial within 12-18 months.

Abstract no: 474
1. Glivec is known as Gleevac or Gleevec in the USA.
2. EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

Further information
Emma Mason (media information officer)
Tel: +44(0)1376 563090 Mobile: +44(0)7711 296 986
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From 16.00 hrs CET Monday 6 November to 14.30 hrs CET Friday 10 November
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18th

Scientists design a PSA-activated protoxin that kills prostate cancer: phase I clinical trial is underway

registration@aacr.org () — Fri, 10 Nov 2006 12:00:00 GMT

Prague, Czech Republic: Scientists have found a way of using a protein made by prostate cancer to target and kill the cancer cells themselves. In preliminary studies the new therapy affected only the prostate, without causing damage to other healthy tissues, and now it is being tested in a phase I clinical trial.

Prostate cancer is one of the commonest cancers in men, with nearly 680,000 new cases each year worldwide and more than 220,000 deaths¹. Furthermore, by the age of 80, approximately 80% of all men will have developed a non-cancerous condition called benign prostatic hyperplasia (BPH) in which the prostate gland becomes enlarged. The findings reported today (Friday 10 November) have the potential to improve the survival and quality of life for men suffering from both these conditions.

Sam Denmeade, associate professor of oncology at John Hopkins University, USA, reported to the EORTC-NCI-AACR² Symposium on Molecular Targets and Cancer Therapeutics in Prague that he and his team³ had developed a protoxin, named PRX302, by modifying an inactive molecule, proaerolysin (PA). They engineered PRX302 to be activated by prostate-specific antigen (PSA) - a protein made in higher than normal levels by prostate cancer. Once activated, they hoped that it would target and kill prostate cancer cells specifically.

He explained: "This represents a different kind of ‘targeted' therapy, in that it seeks to use a protein made by the cancer to destroy itself."

Initial tests in the lab and in animals revealed that when he protoxin was injected into cancerous prostate tissue, it had a significant effect. "In the lab, PRX302 produced significant and often complete regression of the prostate cancer. Since the PSA gene is only found in primates and humans, we then injected either 0.35 or 4.1 micrograms as a single 25 microlitre injection into PSA-producing prostates of cynomolgus monkeys where it resulted in destruction of either 25 or 50% of prostate tissue respectively. This extensive damage was confined to the prostate with no toxicity observed in any other normal tissues, including those adjacent to the prostate such as the bladder, urethra, rectum and seminal vesicles.

Furthermore, two weeks after the injection, we saw a disappearance of the toxin, but the continued presence of dead tissue, suggesting that the toxin's effects could be long lasting.

"Our observations suggest that injections into the prostate of this engineered, PSA-activated protoxin might have potential in treating men with locally recurrent or advanced prostate cancer, or for those with BPH where the protoxin could be used to reduce the size of the enlarged prostate," said Professor Denmeade.

"A phase I clinical trial is in progress now for men with locally recurrent prostate cancer after definitive radiation therapy."

At the moment, the therapy involves injecting the protoxin directly into the prostate. "As such, its application is limited to men with recurrent disease after radiation who still have prostates. If it were to work very well it might be used earlier, in combination with other treatments, most likely radiation. In addition, the toxin is also under consideration as treatment for BPH. We hope that we will be able to further modify the toxin to make a systemic form that could be used to treat advanced prostate cancer in the future."

The study is treating the third cohort of patients and interim results are expected to be available at the end of the year.

PA is an inactive precursor of a bacterial protein that kills cells by forming large pores in the cell membrane. PRX302 kills the cancer cells in the same way when activated by PSA. The idea for this approach to treating prostate cancer came when Prof Denmeade, who had been working for some time on ways to harness the activity of PSA with drugs, heard about PA. "We called Dr Buckley3, who is the world expert on PA, and discussed our strategy. Within two weeks he had generated the toxin and then we tested it for toxicities against a variety of cancers in our lab before starting our studies in prostate cancer."

Abstract no: 526
1. Source: Globocan 2002 at http://www-dep.iarc.fr/
2. EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
3. Protox Therapeutics Inc., a spin-off company that was formed following the promise shown by PRX302 in early studies, has worked with Professor Denmeade in completing the pre-clinical studies and initiating the phase I clinical trial. Dr Tom Buckley, of the University of Victoria, Canada, is a co-founder of Protox.

Scientists harness diptheria toxin and interleukin 2 to help the immune system attack melanoma in humans: phase II trial continues

registration@aacr.org () — Thu, 09 Nov 2006 12:00:00 GMT

Prague, Czech Republic: Researchers investigating ways of prompting the immune system to recognise and kill tumour cells have found that a drug containing parts of the diptheria toxin appears to work well in patients with advanced melanoma (skin cancer). In the first part of a phase II clinical trial to test the drug denileukin diftitox (also known as DAB(389)IL2 or ONTAK) in melanoma, five out of seven patients with stage IV disease experienced significant regression or stabilisation of both tumours and metastases. The two other patients in whom the disease progressed were on a lower dose of the drug. All the patients are still alive after 12 months.

Dr. Jason Chesney, associate director for translational research at the JG Brown Cancer Center, University of Louisville, Kentucky, USA, told a news briefing at the EORTC-NCI-AACR¹Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Thursday 9 November): "We are seeing some exciting results in stage IV melanoma patients whose median life expectancy is normally only about eight months. The phase II trial is continuing to examine the efficacy of denileukin diftitox in patients with melanoma."

The immune system that attacks cancer cells in humans depends on a balance between T cells, which specifically recognise and attack antigens such as tumour cells, and suppressive or regulatory T cells (Tregs), which turn off activated immune cells in order to prevent autoimmunity.

Dr. Chesney explained: "Recently a subset of regulatory T cells has been found to directly suppress the activation of the anti-tumour T cells, but it was also discovered that, if the Tregs were depleted by targeting them with denileukin diftitox, then particular T cells in the immune system known as CD8+ T lymphocytes were able to attack and kill the melanoma cells in mice."

Denileukin diftitox is a fusion protein made up of amino acid sequences for the diptheria toxin and the T cell growth factor, interleukin 2 (IL2). It targets Tregs that have IL2 receptors on their cell surface, and it binds to part of the receptor called CD25. Once it reaches the inside of the cell it prevents protein synthesis, which leads to cell death within hours.

"We thought that if denileukin diftitox could selectively deplete Tregs in patients with melanoma, this would allow the CD8+ T cells to do their job of recognising and attacking the melanoma cells," said Dr. Chesney.

Dr. Chesney and his colleagues gave seven patients with stage IV melanoma nine or twelve micrograms per kilogram of body weight daily for four days, every three weeks for four cycles. The two patients on the lower dose had newly detectable tumours and tumour growth after two cycles. However, the five patients on the higher dose experienced significant regression of several metastatic tumours after four cycles, including subcutaneous tumours and metastases in the liver and lymph nodes.

One patient had two tumours on the leg that had died and became infected, requiring surgery. When the researchers examined the tumour tissue they found that it was surrounded by CD8+ T lymphocytes. "This meant that the lymphocytes had been successfully activated to attack the tumour, which consequently had died. We also found that the concentration of Tregs in this patient decreased by more than a half after the second day's dose of denileukin diftitox," said Dr. Chesney.

"To our knowledge, this is the only trial to study the effects of Treg depletion in human cancer patients. From the results, we conclude that depleting Treg cells in patients with melanoma may allow the immune system to be activated successfully to kill cancer cells. These patients have survived longer than the median average life expectancy of a patient with stage IV melanoma.

"We also believe that, in the future, immunotherapies that depend on depleting Treg cells may prove to be useful in all types of cancer."

Abstract no: 264
1. EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
2. Incidence of melanoma has risen significantly in the past decade and now affects about one in 74 people in the USA. In 2006 it is expected to kill 41,000 people worldwide.

Further information
Emma Mason (media information officer)
Tel: +44(0)1376 563090 Mobile: +44(0)7711 296 986
Email: wordmason@mac.com
From 16.00 hrs CET Monday 6 November to 14.30 hrs CET Friday 10 November
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Systemic treatment before surgery for kidney cancer prolongs patients’ survival

registration@aacr.org () — Thu, 09 Nov 2006 12:00:00 GMT

Prague, Czech Republic: Preliminary results from a phase II clinical trial have provided the first evidence that treating people with kidney cancer with bevacizumab and erlotinib¹ before surgery is safe, effective and may prolong patients' survival.

Renal cell carcinoma² (kidney cancer) is notoriously hard to treat, especially once it has started to spread to other sites in the body. If it has metastasised to the lymph nodes, five-year survival is between 5-15 per cent and if it has spread to other organs the five-year survival is less than five per cent.

Studies have been carried out investigating the use of targeted therapies, such as bevacizumab and erlotinib, after surgery, but researchers at the University of Texas MD Anderson Cancer Center, USA, are conducting the first trial to investigate their use before surgery.

Assistant professor of medicine, Eric Jonasch, told a news briefing at the EORTC-NCI-AACR³ Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Thursday 9 November) that, as of June 2006, the 20 patients enrolled in the trial within the previous year were all still alive. One had complete remission in the primary tumour and stable disease in bone metastases, three patients were in partial remission, 13 patients had stable disease and three patients had progressive disease.

"Without this treatment I would have expected most of them to have progressive disease by now," said Prof Jonasch. "The average time to progressive disease is usually about twelve weeks, and I would argue that our patients have more aggressive disease as they have not had the benefit of any previous treatment.

"These early data suggest pre-surgical treatment with bevacizumab and erlotinib is safe and efficacious in patients with previously unresected, untreated metastatic renal cell carcinoma, with shrinkage of both the metastatic disease and primary tumours.

"Our findings indicate that this treatment approach might be applicable to a wide range of patients with renal cell carcinoma, and that we might be able to use systemic treatment, before surgery, to treat many more people with metastatic disease successfully. It could become a new paradigm of treatment for the disease, instead of the current up-front surgery followed by systemic therapy."

Prof Jonasch and his colleagues aim to enrol a total of 50 patients in the study, which they hope to complete by early 2007. So far they have 32 patients, and have evaluated tissue from 20. The patients were previously untreated, did not have brain metastases and had not undergone kidney surgery.

They gave the patients bevacizumab intravenously once every two weeks for four doses, and erlotinib orally every day for eight weeks. Two weeks after the last dose of erlotinib and four weeks after the last dose of bevacizumab, they surgically removed the kidney tumour (cytoreductive nephrectomy). Patients who had stable disease or a response one month after the surgery were restarted on the treatment, which was continued until the cancer started to progress.

When the researchers looked at the protein expression of key signalling molecules involved in controlling cell proliferation, survival and migration, they could not find any difference between tissues from treated patients and tissues from their tissue bank which had come from untreated patients. The one exception was a slight increase in the expression of AKT in the treated group, which meant that blocking the VEGF signalling pathway with bevacizumab might have resulted in feedback to the AKT pathway, which is known to be involved in cell signalling.

"At the moment, we don't understand what mechanisms are operating to bring about the response we have observed in patients," said Prof Jonasch. "We are looking at a number of other biomarkers to look for a ‘signal' that can be associated with the response. We want to discover how these targeted therapies produce a response in renal cell carcinoma, what molecules and genes are controlling disease resistance and response, and, specifically, what role is played by the protein VHL, which is frequently mutated in patients with kidney cancer and which is known to be an important driver of angiogenesis."

In addition, Prof Jonasch and his team are running similar trials with two other targeted therapies, sorafenib and sunitinib.

He said: "The main aim of this study was to look at the efficacy and safety of using these targeted therapies before surgery, and our results have shown that there were few side effects and that it prolonged the survival of our patients."

Abstract no: 250
1. Bevacizumab is a monoclonal antibody that inhibits angiogenesis; it is marketed as Avastin. Erlotinib targets EGF, blocking the signal that tells cells to divide; it is marketed as Tarceva.
2. Renal cell carcinoma is more common in men than in women, affecting an average of 4.7 men and 2.5 women in every 100,000 in the world (age standardised rate, world), and killing an average of 2.3 men and 1.2 women in every 100,000 (ASR, world). It is much more common in developed countries, with an average incidence of 10.4 per 100,000 in men, compared to 2.1 per 100,000 in less developed countries. (Source: Globocan 2002)
3. EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

Further information
Emma Mason (media information officer)
Tel: +44(0)1376 563090 Mobile: +44(0)7711 296 986
Email: wordmason@mac.com

From 16.00 hrs CET Monday 6 November to 14.30 hrs CET Friday 10 November
EORTC-NCI-AACR symposium press office:
Tel: +420 261 177 006 Fax: +420 261 177 025

Scientists discover way to block growth of prostate cancer cells

registration@aacr.org () — Wed, 08 Nov 2006 12:00:00 GMT

Prague, Czech Republic: Scientists have discovered for the first time a specific biochemical pathway by which the sex hormone, androgen, increases levels of harmful chemicals called reactive oxygen species (ROS) in the prostate gland that play a role in the development of prostate cancer. They found that a drug that blocks this pathway significantly prolonged survival and inhibited tumour development in mice that were genetically engineered to spontaneously develop prostate cancer and die of the disease. The hope is that this drug could be used eventually to treat men at high risk of developing prostate cancer and to prevent recurrences in men already treated for primary tumours.

Dr. Hirak Basu told a news briefing at the EORTC-NCI-AACR¹ Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Wednesday 8 November): "Previous work has demonstrated that androgen treatment increased reactive oxygen species levels in androgen-dependent prostate cancer cells, but, until now, the pathway involved was unknown."

Dr. Basu is an associate scientist and principal investigator in the Prostate Cancer Group at the Paul P. Carbone Comprehensive Cancer Center, Madison, WI, USA. He and his collaborators at the centre found that levels of a key enzyme, spermidine/spermine acetyl transferase (SSAT), which starts oxidation of polyamines, rose markedly when prostate cancer cells were treated with androgen. Polyamines are small molecules produced in large quantity by the prostate gland and are secreted in the seminal fluid. Oxidation of polyamines generates a large amount of the ROS, hydrogen peroxide. Peroxide causes oxidative stress, a condition in which cells produce an excess of oxygen-free radicals, which are known to play a key role in cell signalling and prostate cancer development.

"These results demonstrate that polyamine oxidation is one of the major causes of androgen-induced oxidative stress in prostate cancer cells," said Dr Basu. "The discovery of this pathway is a major step forward in understanding the role of androgen in prostate cancer development."

"Many scientists in the polyamine field have worked towards increasing, rather than decreasing, oxidative stress in order to destroy established tumours. However, no one that I know has tried to reduce oxidative stress by blocking polyamine oxidation to prevent prostate tumours, and this is what we set out to do."

Having discovered the role played by polyamine oxidation, the researchers with the help of their collaborators at Wayne State University, Detroit, MI, USA, synthesised a molecule called MDL 72,527 (MDL), which was previously known to be an inhibitor of acetyl polyamine oxidase (APAO). APAO catalyses the oxidation of acetyl polyamines produced by SSAT - the process that results in the generation of ROS. MDL can, therefore, block androgen-induced ROS production in prostate cancer cells.

They injected MDL into the genetically engineered mice and found that it inhibited polyamine oxidation and reduced oxidative stress in the prostate glands of the animals. The treatment significantly increased overall survival and delayed time to prostate tumour development. In repeat experiments, between 50-60% of mice treated with MDL survived ten to twelve weeks longer than the untreated control group.

"To the best of our knowledge, this is the first report of a specific enzyme inhibitor MDL that blocks androgen-induced oxidative stress in the prostate and prevents spontaneous prostate tumour development," said Dr Basu.

More tests have to be carried out, but the researchers, working with the world-renowned prostate cancer clinician Dr George Wilding (a co-author of the paper), hope that phase I clinical trials of MDL might be able to start in 12-18 months.

Dr Basu said: "After surgery and radiotherapy for the primary tumour, breast cancer patients can be treated with several drugs such as tamoxifen and aromatase inhibitors that prevent or delay breast cancer recurrence. No such treatment exists for prostate cancer patients. After treatment of their primary tumours, prostate cancer in men is managed by watchful observation only. The immediate goal of our research is to develop agents such as MDL to fill this unmet medical need. If MDL, or any of the other agents that we are working with, can be expanded further to treat all high-risk men, we will be delighted."

Abstract no: 122
1. EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

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Vaccination with embryonic stem cells prevents lung cancer in mice

registration@aacr.org () — Wed, 08 Nov 2006 12:00:00 GMT

Prague, Czech Republic: Researchers in America have discovered that vaccinating mice with embryonic stem cells prevented lung cancer in those animals that had had cancer cells transplanted into them after the vaccination or that had been exposed to cancer-causing chemicals.

The findings suggest that it could be possible to develop embryonic stem cell vaccines that prevent cancers in humans, such as hereditary breast and colon cancer and lung cancer caused by smoking or other environmental factors.

Professor John Eaton told a news briefing at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Wednesday 8 November): "We found that the vaccinations were between 80-100% effective in preventing tumour growth in mice that were subsequently challenged with transplanted Lewis lung carcinoma, and it was between 60-90% effective in mice subsequently exposed to carcinogens that cause lung cancer.

"Our results raise the exciting possibility of developing a prophylactic vaccine capable of preventing the appearance of various types of cancers in humans, especially those with hereditary, chronological or environmental predispositions to neoplastic disease." However, he warned that the work was still in its early stages and that people should not think that, for instance, they could start, or carry on, smoking because a vaccine to prevent lung cancer was just around
the corner.

"Cancer has been prevented and even cured in mice hundreds of times. At present, all I can say is that so far it looks good, and that, unless something unexpected happens, this strategy might some day be applied to humans at high risk for development of cancer. The likelihood of this happening is more a question for the US Food and Drug Agency than for us. Given their stringent regulations I consider it quite likely that, by the time this is tried in humans, I will be pushing up daisies."

Prof Eaton is the James Graham Brown Professor of Cancer Biology and Deputy Director of the James Graham Brown Cancer Center, University of Louisville, USA. He and his colleague, Dr Robert Mitchell, tested two different vaccines in the mice. One consisted of embryonic stem cells (ESC) only, obtained from mouse blastocysts (very early, pre-implantation embryos). The other vaccine consisted of the ESCs combined with cultured fibroblast cells producing GM-CSF, a growth factor usually made by white blood cells and blood vessel-lining endothelial cells, which "supercharges" the immune response and appears to enhance the vaccine-induced immunity to cancer.

Prof Eaton explained: "We needed a delivery vehicle for GM-CSF and chose STO fibroblasts because they are often used as a 'feeder layer' to maintain these particular mouse embryonic stem cells in their embryonic state. If we had used only ESCs expressing GM-CSF, they might have differentiated into non-embryonic cells, which, therefore, would not have worked as a vaccine."

He and his team injected mice with ESCs alone or ESCs + STO/GM-CSF. In mice that had Lewis lung carcinoma transplanted into them afterwards, ESCs were 80% effective in preventing tumour growth and ESCs + STO/GM-CSF were 100% effective. In mice subsequently exposed to a carcinogen that causes lung cancer (3-methylcholanthrene followed by repetitive dosing with butylated hydroxytoluene), ESCs resulted in 60% of mice remaining tumour free after 27 weeks and ESC + STO/GM-CSF resulted in 90% remaining tumour free. Importantly, tumours arising in vaccinated mice were, on average, about 80-90% smaller than tumours in unvaccinated mice. All the unvaccinated mice developed tumours. None of the vaccinated mice developed autoimmune disease or a showed a significant decline in adult pluripotent bone marrow stem cells - both potential adverse responses to the vaccinations.

Prof Eaton said: "We think the results from the carcinogen-initiated cancers are probably the most important, as they are closer to the ‘real-life' model of the development of cancer than just implanting cancer cells in an animal. We are studying several different types of carcinogen-induced mouse cancers (skin, colon, breast) to determine whether the preventative effect of vaccination extends beyond our models of lung cancer (although in our state of Kentucky with its high smoking rates, lung cancer alone would be a big victory). We may also vaccinate ageing rodents, the majority of which develop endocrine tumours in old age.

"In terms of human testing, if all goes well, then I think this vaccination might best be tested in women at high (genetic) risk of breast cancer, in people with high (genetic) risk of colon cancer and, perhaps, in smokers."

"Our progress over the next few years will depend, to a large extent, on whether we can attract significant funding. Our work is presently supported by a pilot grant from our cancer centre and a small grant from the Kentucky Lung Cancer Research Program. US federal funding agencies such as the NIH - notorious for funding predictable research - have been quite disinterested."

Abstract no: 29
1. EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

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Enzyme inhibitor produces stable disease in patients with advanced solid cell cancers: phase II trials initiated

registration@aacr.org () — Wed, 08 Nov 2006 12:00:00 GMT

Prague, Czech Republic: Preliminary trials of a MEK enzyme inhibitor have shown that it is capable of producing long-lasting stable disease in patients with advanced solid cancers. Tests showed that the drug inhibited key targets in the patients' tumours, and now it is being tested in phase II clinical trials. Professor Alex Adjei told the EORTC-NCI-AACR¹ Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Wednesday 8 November) that the drug AZD6244 (ARRY-142886)² inhibited MEK1/2 - an enzyme that plays an important role in the Ras/Raf/MEK/ERK cell signalling pathway, which regulates cell proliferation and survival. Activation of this pathway has been implicated in a number of cancers, including lung, pancreatic, colon, melanoma and thyroid cancer.

"Laboratory studies have shown that AZD6244 has an effect on human tumours at nanomolar concentrations, and the first part of the phase I clinical trial has determined the maximum tolerated dose and the safety of the compound. Results from this second part of the trial demonstrate that a dose of 100mg of AZD6244 is well tolerated, produces a high incidence of long-lasting stable disease, and is associated with a profound inhibition of the cell signalling protein pERK and a reduction in cell proliferation - which indicates that the drug is working against the tumours," said Prof Adjei, who was professor of oncology at the Mayo Clinic, Rochester, USA, before moving in October to be the senior vice-president for clinical research and chair of the Department of Medicine at the Roswell Park Cancer Institute, Buffalo, USA.

Prof Adjei and his colleagues at the Mayo Clinic, University of Colorado Health Sciences Center and Fox Chase Cancer Center recruited 34 patients with advanced cancers, including melanoma, breast, lung and colorectal cancers. Approximately 40% of the patients had melanoma. The researchers were particularly interested in this tumour type because a large proportion harbour B-Raf mutations, and tumours with these mutations may be highly sensitive to MEK inhibitors.

The patients were randomised to receive 100 or 200mg doses, twice a day for 28-day cycles. The larger dose proved to be too high for continuous dosing due to adverse side effects, but the smaller dose was well tolerated over a prolonged period.

The researchers tested biopsy tissue taken from the patients both before and after dosing. They found that the pERK protein was reduced by 77%. They also looked at another protein, Ki-67, which is used as a marker for cell proliferation. After dosing, there was a reduction in Ki-67 in nine out of 20 patients, and in five of those nine patients the reduction was at least 50% or more.

"We found that after 15 days of dosing, AZD6244 continued to inhibit pERK at times when concentrations of the drug in the blood were at their lowest levels between doses. At the lowest concentration, 400 nanograms of the compound per microlitre of plasma still corresponded to a 35-44% inhibition of pERK," said Prof Adjei.

Overall, 39 of 57 patients completed at least one cycle of treatment with AZD6244. After completion of the second cycle, 19 (49%) had stable disease, and nine of these patients (six melanoma, one each of breast cancer, non-small cell lung cancer and medullary thyroid cancer) remained stable for five or more months (range, 5-14+ months; median, 6 months). Two patients, one with thyroid cancer and the other with melanoma, continue to receive treatment with AZD6244 after one year. Sixteen of the 20 patients with melanoma completed at least one cycle of treatment. Twelve had stable disease after completion of cycle two, with stable disease persisting for at least five months in six patients (range, 5 - 13+ months; median, 6.5 months).

Prof Adjei said: "This drug shows initial promising results. It appears to be able to target cancers with over-activation of MEK and associated cell signalling pathways in an efficient manner. Furthermore, it is easy to give to patients as it comes in liquid-soluble powder form, which can be swallowed. As a result, a number of phase II clinical trials have been initiated in patients with melanoma, pancreatic, lung and colon cancers."

Abstract no: 26
1. EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
2. AZD6244 (ARRY-142886), an MEK inhibitor, was invented by Array BioPharma and is being
co-developed with AstraZeneca. Array BioPharma sponsored Prof Adjei's study.

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Stephen S. Hecht Honored with AACR-Cancer Research and Prevention Foundation Award For Ground-breaking Research on Tobacco and Cancer

registration@aacr.org () — Mon, 06 Nov 2006 12:00:00 GMT

PHILADELPHIA -- Stephen S. Hecht, an internationally recognized expert on cancer-causing agents in tobacco and the pathways by which they cause cancer, has been selected to receive the fifth annual American Association for Cancer Research (AACR)-Cancer Research and Prevention Foundation (CRPF) Award for Excellence in Cancer Prevention Research.

Dr. Hecht, the Wallin Professor of Cancer Prevention and the American Cancer Society Research Professor at The Cancer Center at the University of Minnesota, is being honored for more than three decades of research on tobacco and its link to cancer formation and growth.

Over this span of time, Dr. Hecht has been the most cited author on tobacco carcinogenesis, and is generally recognized as the world's leader in research on tobacco-specific human carcinogens called nitrosamines, found in cigarette smoke and smokeless tobacco. Other work in his laboratory, showing that exposure to second-hand tobacco smoke resulted in the presence of tobacco-specific carcinogens in nonsmokers has had a profound impact on clean indoor air laws critical for tobacco control.

"Stephen Hecht's ground-breaking and detailed research on tobacco-specific nitrosamines has enhanced our understanding of tobacco carcinogenesis," said Dr. Margaret R. Spitz, chair of the Department of Epidemiology at The University of Texas M. D. Anderson Cancer Center and co-chair of the award selection committee.

"His research has provided a strong scientific rationale for public policies on smoking restriction."

Added Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR: "Dr. Hecht has been, and continues to be, among the most recognized scientists in the world studying the impact of tobacco and tobacco products on lung cancer. His critical work in this field - marked by its thoroughness, breadth and extraordinary high quality -- is helping to save countless lives from this devastating disease."

It was 1974 when Dr. Hecht, along with Dr. Dietrich Hoffmann, provided the first demonstration of organic carcinogens - nitrosamines -- in unburned tobacco. The two scientists identified substantial amounts of a specific nitrosamine called N'-nitrosonornicotine (NNN) in unburned tobacco, suggesting that smokeless tobacco was not a harmless substitute for cigarettes. This work ultimately led to the regulation of smokeless tobacco products.

Dr. Hecht subsequently reported the first synthesis of another nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and he demonstrated its formation from nicotine during the curing process. He further showed that exposure to NNK resulted in lung cancer in laboratory mice and rats, and then characterized how NNK caused lung cancer. In highly detailed studies, Dr. Hecht determined virtually all the known pathways of metabolism of NNK, and later showed the chemical binding of DNA to metabolically activated NNK, NNN and other tobacco-related nitrosamines - steps that are critical to the initiation of cancer.

These studies led to the development of biomarkers - substances that can be measured in blood or urine - to help identify individuals most susceptible to the cancer-causing effects of tobacco products. Such biomarkers also can help determine exposure of non-smokers to second-hand tobacco smoke. Dr. Hecht demonstrated the presence of a metabolite of NNK in the urine of non-smokers exposed to second-hand tobacco smoke in various settings. The metabolite, NNAL, also was discovered in the fetuses and newborns of smoking mothers. Such evidence provided the rationale for tobacco control laws in public places.

Another area of research in the Hecht lab is the identification and development of naturally occurring chemopreventative agents that may help protect smokers from later disease. Current work in this area involves compounds found in cruciferous vegetables, nuts and fruit. Phase II studies to evaluate the efficacy of these agents in smokers and ex-smokers are now being planned.

Other past winners of AACR-CRPF Award for Excellence in Cancer Prevention include 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.

Dr. Hecht graduated from the Duke University, with a degree in chemistry. He was awarded a Ph.D. in organic chemistry from the Massachusetts Institute of Technology, where he also did postdoctoral research in mass spectrometry. Prior to moving to the University of Minnesota in 1996, for 23 years Dr. Hecht conducted research at the American Health Foundation in Valhalla, N.Y., where he was Director of Research from 1987-1996. At the University of Minnesota, he is Head of the Carcinogenesis and Chemoprevention Program at the Cancer Center, Co-director of the Transdisciplinary Tobacco Use Research Center, and a member of the Medicinal Chemistry graduate department.

Dr. Hecht, who has authored or co-authored more than 600 publications, holds a Merit Award and was previously the recipient of an Outstanding Investigator Grant, both from the National Cancer Institute. In 2000, he was named an American Cancer Society Research Professor, one of about 40 in the country. Dr. Hecht has served on several International Agency for Research on Cancer working groups, was a contributor to the 2005 Surgeon General's Report on Passive Smoking and Health, and is chapter editor for cancer in the upcoming Surgeon General's Report on How Tobacco Causes Diseases. He also has participated on numerous government and international committees including the National Cancer Institute's Board of Science Counselors, the National Toxicology Program Board of Scientific Counselors, and the National Center for Toxicological Research Science Advisory Board.

He is active in the AACR, where he has served on program committees for national and special meetings, and on the steering committee of the Chemistry in Cancer Research Working Group.

Dr. Hecht will give an award lecture titled, "A Tobacco-Specific Lung Carcinogen: from Basic Research to Tobacco Control," on Tuesday, November 14, at the Fifth Annual AACR International Conference on Frontiers in Cancer Prevention Research. This premier meeting on cancer prevention research will be held November 12-15, 2006 at the Hynes Convention Center in Boston, Mass.

# # # #

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 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:
Warren R. Froelich
215-440-9300 ext. 198
froelich@aacr.org

HPV Test is a Better Long-Term Predictor of Cervical Cell Abnormalities Than Pap Smear

registration@aacr.org () — Wed, 01 Nov 2006 12:00:00 GMT

PHILADELPHIA - The best initial cervical cancer screening tool for younger women is still the traditional Pap smear. However, a large Danish study has found that for older women (age 40 and older), a test for human papillomavirus (HPV) is a much more effective way to screen for potential cancer.

The reason, report researchers in the November 1 issue of Cancer Research, is that HPV infection is both frequent and transient in younger women, and they would often test positive for HPV when no actual risk of cervical cancer existed. But, in older women, HPV infection is rarer and more persistent, putting a woman at substantial risk for the disease before changes in cervical cells, detected by Pap smears, are obvious.

"We have documented that a single HPV test can actually predict older women at risk for cervical cancer better than a single Pap smear can," said the study's senior author, Susanne Krüger Kjaer, M.D., professor and head of the Department of Virus, Hormones and Cancer at the Danish Cancer Society.

The researchers specifically found that the absolute risk of developing cervical cancer in an older woman who tests positive for HPV is greater than 20 percent within a 10-year period. They also note that most women who test positive for HPV also test negative on a Pap smear given at the same time.

"Based on these results, we feel that an HPV test would benefit older women, whether or not that test is used in conjunction with Pap smears, or used by itself as an initial screen," Kjaer said.

Pap smears (also known as cervical cytology) look for abnormalities in the appearance of cells lining the cervix and have long been the primary screening tool for cervical cancer. The test has led to significant declines in both the incidence and morbidity of the disease in the U.S. Some strains of HPV (which includes more than 100 different viruses) are now recognized as the major cause of cervical cancer. The federal Food and Drug Administration (FDA) has approved use of the HC2 High-Risk HPV DNA Test for women who had abnormal Pap test results.

In 2003, the FDA allowed the HC2 test, which checks for 13 high-risk HPVs, to be used for screening in conjunction with the Pap smear in women over the age of 30.

Each of the screening tests has its limitations, Kjaer says. Several studies have shown Pap smears to be only modestly accurate, with a sensitivity (ability to correctly identify lesions) that is lower than generally believed, she said. The HPV test is more sensitive than a Pap smear, but has a relatively lower specificity, meaning that it isn't as able to detect truly negative cases, Kjaer said.

However, the majority of women who test positive for HPV actually has a concurrent negative Pap smear, Kjaer says, and it has been uncertain how truly at risk they are for developing cervical cancer.

To find out how effective the HPV test was at predicting that risk, Kjaer and her colleagues used two Danish population-based prospective cohorts-one included 8,656 women aged 22-32, and the other enrolled 1,578 women who were 40-50 years old. At enrollment in the study these women had cytology; cervical samples for HPV testing were also collected. These samples were stored and later tested for HPV using the HC2 test. The women were followed with a number of Pap smears over the course of 10-plus years.

The researchers found that among women 40-50 years old who had a positive HPV test and a negative Pap smear, nearly 25 percent developed cervical abnormalities within 5 years; after 10 years, more than 35 percent experienced an abnormal Pap test. Younger women who were HPV positive and Pap smear negative also had a high absolute risk of subsequent cervical abnormalities - 18 percent after 5 years and 24 percent after 10 years.

Even more important, says Kjaer, was the finding that as many as 21 percent of the older HPV positive women with initially normal cytology subsequently developed histologically confirmed severe changes on the cervix (CIN3 or worse). Conversely, the risk of developing such abnormalities was very low (1.7 percent) among women who tested negative on both screening exams.

"This shows that the HPV test was better than a Pap smear at predicting worrisome changes in the cervix over time," Kjaer says.

But the researchers also found two other important factors. One is that HPV infection was much more common in the younger women (17 percent) compared to the older women (3.6 percent) and that in the older women, a much higher percentage of the abnormalities were regarded as severe.

"This reflects the phenomenon that HPV infection among younger women is mostly transient, and therefore causes mostly mild changes, whereas in older women a higher proportion of the infections are persistent, and more likely to induce more severe cellular change," she said.

Given the findings, coupled with the frequency of infection, Kjaer said clinicians may find it beneficial to screen younger women with a Pap smear and follow up on positive results at a given level with an HPV test, and offer HPV testing to older women as a stand-alone screening test, or in conjunction with a Pap smear.

"Since even a single positive HPV test is substantially predictive of future cellular changes in the cervix, it can help stratify women in different risk categories," she said.

Editors Note: For a PDF of this study, please click 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 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:
Warren R. Froelich
215-440-9300 ext. 198
froelich@aacr.org

Major Gift Doubles Grantmaking for Pancreatic Cancer Research

registration@aacr.org () — Fri, 27 Oct 2006 12:00:00 GMT

PHILADELPHIA - The American Association for Cancer Research today announces a $635,000 gift from the Pancreatic Cancer Action Network (PanCAN) which significantly increases its grantmaking potential for young cancer scientists.

The major gift establishes the AACR-PanCAN Fellowship for Pancreatic Cancer Research, and increases the number of AACR-PanCAN Career Development Awards for Pancreatic Cancer Research from three to six. It is the largest annual gift in PanCAN's five-year philanthropic partnership with the AACR.

"PanCAN is proud to partner with AACR to provide six Career Development Awards and one Fellowship Award this year for young investigators in the field of pancreatic cancer research," said Julie Fleshman, President and CEO of PanCAN. "AACR's superb peer-review system and rigorous approach to science ensures that our investments are supporting science that is innovative and progressive. These scientists are providing hope to the pancreatic cancer community and we strongly believe that their efforts will help move the science toward better diagnosis and treatment of this devastating disease."

With the PanCAN awards, the AACR has available to early career investigators eight Career Development Awards and nine Research Fellowships totaling $1,240,000 in 2007. Awards such as these provide important transitional support for direct research expenses as researchers move from the ranks of early-career scientists to faculty status.

AACR Career Development Awards are open to junior faculty who, at the start of the grant term, are in the first, second, or third year of their first full-time appointment after completing post-doctoral studies, at an academic or medical institution. Eligible positions include instructor, acting assistant professor, research assistant professor, assistant professor, or an equivalent full-time appointment. The awards provide two-year grants of $50,000 per year for direct research expenses. This year one of the awards, the Seena Magowitz Career Development Award, is specifically targeted to translational research.

AACR Research Fellowships are open to postdoctoral fellows and clinical research fellows at an academic facility, teaching hospital, or research institution who will be in the first, second, or third year of their postdoctoral training at the start of the fellowship term. The Samuel Stroum Fellowship will provide a one-year grant of $35,000 to support the salary and benefits of the Fellow.

Applications must be submitted online through proposalCENTRAL by December 1, 2006. The grant terms begin on July 1, 2007. Winners must attend the 2007 AACR Annual Meeting in Los Angeles, Calif. to accept the award.

For further information on the awards or a complete list of supporters, please visit the AACR's 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 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 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.

Media Contact:
Angela DeCicco
215-440-9300 ext. 104
decicco@aacr.org

Program Contact:
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ozard@aacr.org

Grape Seed Extract Halts Cell Cycle, Checking Growth Of Colorectal Tumors In Mice

registration@aacr.org () — Wed, 18 Oct 2006 12:00:00 GMT

PHILADELPHIA - Chemicals found in grape seeds significantly inhibited growth of colorectal tumors in both cell cultures and in mice, according to researchers who have already demonstrated the extract's anti-cancer effects in other tumor types.

Their study, published in the October 15 issue of Clinical Cancer Research, documented a 44 percent reduction of advanced colorectal tumors in the animals, and also revealed, for the first time, the molecular mechanism by which grape seed extract works to inhibit cancer growth. The authors found that it increases availability of a critical protein, Cip1/p21, in tumors that effectively freezes the cell cycle, and often pushes a cancer cell to self destruct.

"With these results, we are not suggesting that people run out and buy and use grape seed extract. That could be dangerous since so little is known about doses and side effects," said Rajesh Agarwal, Ph.D., professor in the Department of Pharmaceutical Sciences at the University of Colorado Health Sciences Center in Denver.

"The value of this preclinical study is that it shows grape seed extract can attack cancer, and how it works, but much more investigation will be needed before these chemicals can be tested as a human cancer treatment and preventive," he said.

The skin and seeds of grapes are a rich source of proanthocyanidins, a class of antioxidant flavonoids that remove harmful free oxygen radicals from cells. Grape products (juice and red wine) are known for their heart healthy effects, especially in lowering levels of blood cholesterol, Agarwal said, and because grape seeds contain higher concentrations of these chemicals, they are widely marketed as a dietary supplement.

Agarwal and his team of investigators were first to report, in 1999, that grape seed extract also has chemopreventive activity against skin cancer. Their subsequent preclinical work has shown that the extract also retards growth of prostate cancer cells.

In this study, Agarwal tested the extract on colorectal cancer, the second most common malignancy in Americans as well as the second leading cause of cancer deaths in this country. They exposed two different human colon carcinoma cells to the extract, and found a dose- and time-dependent inhibition of cell growth.

"Beneficial effects were correlated with how much extract was used and how long it was used for," Agarwal said. The number of live cells decreased by 92 percent in one cell line when the highest dose was given for the longest time period, which was two days, he said.

The researchers then performed a cell cycle distribution analysis, looking to see specific growth inhibitory effects. They found that the longer the extract was used, the more cells were "arrested" in the G1 phase of the cell cycle, the time when the cell is preparing to duplicates its DNA before dividing, and, correspondingly fewer cells had advanced to the "S" phase, when DNA is being actively duplicated.

They then studied the extract's effect on the molecular regulators that control the cell cycle, and found a strong dose-dependent increase in Cip1/p21 protein. In fact, the amount of Cip1/p21 protein within the cells increased by more than 150 times after 12 hours of treatment, Agarwal said. The researchers also noted a corresponding decrease in a number of different cyclin proteins and associated cyclin-dependent kinases (CDKs).

This all makes sense, according to Agarwal. One of the hallmarks of cancer is rampant cell growth due to loss of control of the cell cycle, and CDKs help push the cycle from a quiet state through to cell division. The Cip1/p21 protein, however, is powerful enough to inhibit the activity of CDKs and can also control apoptosis, or programmed cell death, he said.

"This protein physically interacts with CDKs," Agarwal said. "In normal cells, it attaches to CDKs to inhibit growth, but if a cell wants to grow, as it does in cancer, levels of Cip1/p21 are reduced, or non-functional."

Indeed, further experimentation demonstrated that grape seed extract increased the level of Cip1/p21 protein, allowing it to bind to and shut down the CDKs driving the cell cycle. The investigators also found that the extract can do that even if a cancer cell is missing p53 function (which also helps controls the cell cycle).

"That is good news, because most cancers are missing p53," Agarwal said.

Finally, the researchers tested the extract in mice. They implanted the animals with advanced human colorectal cancer cells and at the same time, gave the mice grape seed extract through a feeding tube. They tested only one dose, which was larger than a human would comparatively use, Agarwal said, and after eight weeks, tumor volume in treated mice were reduced by 44 percent and tumor weight by 33 percent, compared to control animals. No toxic side effects were observed in treated mice, despite the high doses.

Similar to the cell culture studies, Cip1/p21 protein levels increased in tumors in mice treated with grape seed extract, Agarwal said.

As a first step toward translating their findings into the clinic, the research team now plans to determine the lowest effective, as well as the highest non-toxic doses, by which grape seed extract can offer anticancer benefit in mice.

The study was funded by grants from the National Cancer Institute.

Editors Note: For a copy of this study click 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 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:

Warren Froelich
215-440-9300 ext. 198
froelich@aacr.org

AACR Announces Major Gift for Breast Cancer Research

registration@aacr.org () — Tue, 17 Oct 2006 12:00:00 GMT

PHILADELPHIA - The American Association for Cancer Research today announces a $200,000 gift from the Breast Cancer Research Foundation which will create the BCRF-AACR Fund for Translational Breast Cancer Research.

Announced today at a Breast Cancer Research Foundation research symposium, the gift will be supplemented with a matching grant from the AACR Foundation for the Prevention and Cure of Cancer to create a $400,000 research grant fund for translational breast cancer research. Translational research is defined as a "two-way bridge" that conveys new ideas and discoveries between the laboratory and the clinic, bringing the benefits of basic science knowledge to patients more quickly and effectively. Grants in the amount of $200,000 will be awarded to cancer researchers through AACR's rigorous and competitive scientific review process beginning in 2007.

"The AACR is grateful to the Breast Cancer Research Foundation for this generous gift," said AACR Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.). "This extraordinary generosity ensures that promising cancer research will move forward, with the goals of bringing cutting-edge laboratory research, diagnostic technologies, and individualized treatments to cancer patients as well as exciting new prevention strategies to the public at large."

The American Association for Cancer Research celebrates its 100th anniversary on May 7, 2007. To commemorate this event, the AACR Foundation launched a Centennial Research Grant Campaign in May 2006 with a goal of raising $6 million by May 2009 to support a number of vitally important areas of cancer research. The BCRF gift brings the AACR's Centennial Research Grant Campaign to $2 million.

"We are excited by our new relationship with the Breast Cancer Research Foundation, as such philanthropic partnerships are vital to continuing research. We look forward to working with the BCRF to accelerate progress against breast cancer," Foti said.

The AACR Centennial Fund receives support from a broad range of constituencies, including individuals, foundations, corporations and AACR members. Donated funds are matched by the AACR Foundation's reserve funds to create a larger pool of cancer research grants: contributions to a general "Grant Fund" are matched $2 for every $1 donated; donations to a "Fund for Early-Career Scientists" are matched $4 for every $1 contributed. One hundred percent of Centennial Fund contributions will be awarded as research grants. AACR, with its worldwide brain trust of scientists, is taking a leadership role in making funding for the most promising cancer research a national and international priority.

"This is a time of immense opportunity in cancer research," said AACR President Geoffrey Wahl, Ph.D. "In recent years, there have been a number of significant advances in the prevention, early detection and treatment of cancer, and there are many other promising innovations currently in development. We must make sure that we have sufficient funding to ensure that this promising research advances rapidly."

To contribute to the AACR Centennial Research Grant Campaign, visit www.aacrfoundation.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 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.

Contact:
Staci Vernick Goldberg
215-440-9300 ext. 145
goldberg@aacr.org

AACR CEO Margaret Foti Named to Chamber of Commerce Board

registration@aacr.org () — Fri, 13 Oct 2006 12:00:00 GMT

PHILADELPHIA -- American Association for Cancer Research Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.) was named to the Board of Directors of the Greater Philadelphia Chamber of Commerce. The announcement was made at the Chamber’s Annual Meeting, Oct. 10, 2006.

Foti has dedicated her career to cancer research and the AACR. Progressing through several key editorial and management roles at the AACR, she was appointed to her current position of CEO in 1982 by the AACR’s Board of Directors. In addition, she serves as Secretary-Treasurer and CEO of the AACR Foundation for the Prevention and Cure of Cancer and Managing Editor of Cancer Research. During Foti’s tenure, AACR membership has grown to more than 24,000 scientists residing in more than 80 countries.

In addition to serving as Managing Editor of Cancer Research, the most highly cited cancer journal in the world, Foti and the AACR have launched four additional high-quality journals: 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 scientific pages to the scientific literature every year.

Among her many outside professional activities, 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; and member of the Council of the European Association for Cancer Research. 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.

Foti has received many national and international awards for her contributions to cancer research including: the Association of American Cancer Institutes (AACI) Distinguished Service Award for her outstanding contributions to progress in cancer research; the American Association for Cancer Research service awards; the City of 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; and the American Society of Clinical Oncology Special Recognition Award for her work in advancing clinical cancer research. For her work she 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.

###

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 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.

OBITUARY: HARRIS BUSCH (1923 - 2006)

registration@aacr.org () — Thu, 05 Oct 2006 12:00:00 GMT

PROMINENT CANCER RESEARCHER AND FORMER AACR PRESIDENT
(adapted from the Houston Chronicle )

Harris Busch, M.D., Ph.D -- a prominent cancer researcher and molecular biologist, and past president of the American Association for Cancer Research -- died September 22 of complications from pneumonia at Methodist Hospital in Houston. He was 83.

Dr. Busch, long-time chairman of the Department of Pharmacology at Baylor College of Medicine, specialized in the research of gene control in cancer cells. He was a pioneer in the investigation of cancer cells and was the first to isolate and characterize the nucleus of a cancer cell. He joined the Baylor College of Medicine in 1960 and served for 40 years as its chairman of pharmacology.

Working with surgeon Michael E. DeBakey, Dr. Busch was instrumental in developing the college into an international force for medical scientific research. He helped secure its reputation as one of the top medical schools in the country. Along the way, he wrote over 1,000 scientific articles that appeared in scholarly journals and wrote or edited 30 books. Dr. Busch embodied the American Dream, achieving success after modest beginnings through education and hard work.

Aside from serving as AACR's president from 1989-90, Dr. Busch also was a member of AACR's Board of Directors and the association's public affairs committee. He joined AACR in 1953, attended virtually every Annual Meeting, supported the Annual Meeting Scholar & Training Awards for young investigators, and served as a mentor to many of those scholars.

Born in Chicago, Dr. Busch served in the U.S. Army while attending medical school at the University of Illinois and interned at Cook County Hospital. He joined the U.S. Public Health Service immediately after World War II. In 1945, he married his high school sweetheart, Rose Klora, and for 61 years she was his partner in research and in life. Together they worked and traveled, raised four children and delighted in contradicting each other's stories. They brought their ever-expanding family together at least once a year until Dr. Busch became ill this summer.

In addition to Rose Busch and his children, Daniel Busch, M.D., Laura Smolkin, Ph.D., Gerald Busch, M.D., and Fredric Busch, M.D., Dr. Busch is survived by 12 grandchildren and one great-granddaughter.

Super Chow, Laced With Semi-Synthetic Vitamin E Derivative, Inhibited Spread of Cancer in Mice

registration@aacr.org () — Mon, 02 Oct 2006 12:00:00 GMT

PHILADELPHIA − A chemically altered form of vitamin E mixed into mouse chow dramatically reduced spread of aggressive mammary cancer in mice, suggesting that the compound in pill form could be used to treat human metastatic cancer, according to a report in the October 1 issue of the journal Cancer Research.

The study, by investigators at the University of Arizona, is the first to show that the synthetic compound has potent anti-cancer properties when given in the simplest way possible − as a dietary supplement.

“We tried other ways of delivering different forms of the synthetic vitamin, such as by force feeding and injections, but found that one form, alpha-TEA, was more effective when incorporated into food, and that makes it much more clinically useful,” said the study’s lead investigator, Emmanuel T. Akporiaye, Ph.D., professor in the Department of Immunobiology at the University of Arizona.

Mice eating the super chow had a 4.8-fold reduction in the number of tumors that spread to the lungs, compared to control mice, Akporiaye said. An even greater effect was seen when the animals began eating alpha-TEA-laced food as a cancer preventive, he said.

“These preliminary studies are very promising, and it could be that combining this synthetic vitamin E derivative with other anti-cancer treatments may offer the potential of both treating and preventing human breast cancer,” Akporiaye said.

Although vitamin E (alpha tocopherol) is an anti-oxidant, it cannot destroy tumor cells by itself, he said. To improve the vitamin, derivatives have been created by swapping a hydroxyl chemical group with an acid. One is alpha-tocopheryl succinate (alpha-TOS), which used a succinic acid residue, and another is alpha-tocopheryloxyacetic acid (alpha-TEA), which used acetic acid.

Replacing the hydroxyl group in vitamin E helps force cancer cells to self destruct, Akporiaye said, because the compounds work to free up pro-apoptotic proteins that are normally held in check within cells.

“Cell survival is maintained when pro-apoptotic proteins are confined, and these synthetic forms of vitamin E release them, pushing the cell into committing suicide,” he said. “Only a little part of vitamin E is changed in these synthetic derivatives, but they show amazing anticancer properties, and they selectively target tumor cells,” Akporiaye said.

To make the synthetic vitamins water soluble (not fat soluble like natural vitamin E), researchers have added sodium hydroxide. In this way, these vesiculated forms, called V alpha-TOS and V alpha-TEA, can be delivered clinically through injection or oral gavage (feeding through a tube), and experiments have shown they can treat melanoma, lung and breast cancer in rodent models.

In this study, the Arizona researchers evaluated the anti-tumor effect of V alpha-TOS and V alpha-TEA on mice with an aggressive form of mammary cancer that is similar to human breast cancer that readily metastasizes. They also looked at how well alpha-TEA would affect tumor growth if incorporated into the food (“chow”) that the mice ate.

They found that injecting V alpha-TOS or V alpha-TEA into the peritoneal cavity of the mice reduced the average volume of tumors by two fold, compared to control mice that did not receive the injections. Administering V alpha-TOS daily through a feeding tube had the same effect on tumor size, but V alpha-TOS was ineffective when delivered in this way, Akporiaye said. “We found that V alpha-TOS wasn’t stable, and returned to its natural vitamin E state,” he said.

To gauge the effectiveness of a dietary treatment, the researchers had special rat chow manufactured that incorporated a fairly large quantity of alpha-TEA into the food. They then tested the chow as a cancer preventive and as a cancer treatment.

For the prevention study, the mice ate alpha-TEA chow starting on the same day that they were injected with rodent mammary tumor cells known to spread quickly to the lungs and bones. The mice were allowed to eat as much food as they wanted, and at the end of 29 days, the average tumor volume was reduced by 6.7-fold, compared to control mice who had not been fed alpha-TEA.

In the therapy experiment, mice started eating alpha-TEA chow 11 days after tumors were implanted, and in the experimental group, there was a 3.6-fold reduction in average tumor volume compared to control mice, Akporiaye said.

In both preventive and therapeutic studies, mice fed alpha-TEA chow had a 4.8-fold reduction in the number of tumors that had spread to the lungs, compared to control mice. “The results were very impressive,” he said. “The chow was very effective in slowing down the growth rate of the tumor and significantly reducing metastases.” The alpha-TEA diet produced no visible adverse side effects, not even weight loss, Akporiaye said.

“The combined characteristics of ease of delivery, relevance of route of delivery and selectivity for killing tumor cells suggest that dietary alpha-TEA may be useful for treating metastatic breast cancer,” he said.

The researchers are now testing the effect of reduced doses of alpha-TEA in the chow and plan to test the synthetic vitamin in combination with dendritic cell immunotherapy. “When you kill tumor cells, they release antigens that can be picked up by specialized cells that stimulate the immune system,, and this two-step process could provide a longer lasting outcome,” Akporiaye 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 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 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:
Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

AACR CEO Margaret Foti Receives Cancer Service Award

registration@aacr.org () — Thu, 28 Sep 2006 12:00:00 GMT

PHILADELPHIA – American Association for Cancer Research Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.) will receive the Association of American Cancer Institutes (AACI) Distinguished Service Award for her outstanding contributions to progress in cancer research. The award will be presented during a special ceremony at the AACI’s annual meeting, October 22 – 24, 2006.

“I’m deeply honored to receive this special recognition from the Association of American Cancer Institutes,” Foti said. “The AACI is a vitally important organization in the cancer field. As an effective advocate for the nation’s cancer centers, AACI advances the cancer research agenda and facilitates progress against this terrible disease.”

“Under Dr. Foti’s leadership, the American Association for Cancer Research has become the largest scientific organization in the world focused on every aspect of high-quality, innovative cancer research,” said AACI President H. Shelton Earp III, M.D. “The Distinguished Service Award recognizes her outstanding contributions to the progress of cancer research at the nation’s cancer centers and her commitment to fostering the exchange of knowledge and new ideas among scientists dedicated to cancer research.”

Foti has dedicated her career to cancer research and the AACR. Progressing through several key editorial and management roles at the AACR, she was appointed to her current position of CEO in 1982 by the AACR’s Board of Directors. In addition, she serves as Secretary-Treasurer and CEO of the AACR Foundation for the Prevention and Cure of Cancer and Managing Editor of Cancer Research. During Foti’s tenure, AACR membership has grown to more than 24,000 scientists residing in more than 70 countries.

“Dr. Foti’s accomplishments at AACR are numerous and her exceptional stewardship of AACR has contributed significantly to the U.S. cancer research infrastructure’s status as the best in the world,” said AACI Executive Director Barbara Duffy Stewart.

In addition to serving as Managing Editor of Cancer Research, the most highly cited cancer journal in the world, Foti and the AACR have launched four additional high-quality journals: 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 scientific pages to the scientific literature every year.

Among her many outside professional activities, 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.

Foti has received many national and international awards for her contributions to cancer research including: the American Association for Cancer Research; the City of Paris 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; and the American Society of Clinical Oncology for her work in advancing clinical cancer research. For her work she 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.

# # #

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 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
215-440-9300 ext. 145
goldberg@aacr.org

Potential Diagnostic Marker Indicates Effectiveness of Anti-angiogenic Drugs

registration@aacr.org () — Fri, 15 Sep 2006 12:00:00 GMT

CHICAGO -- If an anti-angiogenic drug is successfully starving a cancer patient’s tumor to death, the number of endothelial cells circulating in the individual’s bloodstream will decrease, thus providing a potential biomarker for gauging the medication’s effectiveness, according to National Cancer Institute (NCI) research.

Previous studies have shown that the blood circulation of cancer patients has an abnormally high number of endothelial cells, which help construct blood vessels including those that feed the cancerous tumor.

“For a cancer to survive, grow and spread, a tumor needs to make more endothelial cells and construct new blood vessels to provide oxygen and other nutrients,” said NCI scientist Haiqing Li, Ph.D., first author of the study.

“In addition to growing them directly from nearby blood vessels, tumors can also signal the body’s bone marrow to boost the supply of endothelial cells in the blood circulation,” Li added.

Results were presented at the first international meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

Anti-angiogenic drugs inhibit blood vessel development at the tumor by killing the endothelial cells lining tumor blood vessels and/or cutting off the supply of endothelial cells from bone marrow. These drugs are typically paired with chemotherapy agents. Unlike anti-angiogenic drugs, chemotherapy agents directly assault tumor cells, and a reliable therapeutic biomarker for evaluating these agents is whether there are fewer cells in the tumor, or more, or just the same amount as before the treatment. Some chemotherapy drugs, Li noted, also have the benefit of being toxic to endothelial cells, providing a possible second biomarker for those agents.

But biomarkers have yet to be defined for anti-angiogenic drugs. “Many anti-angiogenic drugs may encounter problems during clinical studies, because they can't reduce tumor size rapidly like chemotherapies can,” noted Li. “Thus, a biomarker is needed for the effectiveness of anti-angiogenic drugs in an early stage.”

The NCI study, conducted with the European Institute of Oncology (EIO), suggests that the anti-angiogenic drugs enhance chemotherapy’s ability to kill endothelial cells, as indicated by increases in dead endothelial cells circulating in the patient’s blood stream.

The NCI and EIO scientists also discovered that anti-angiogenic drugs might combat cancer by preventing immature cells in the bone marrow from developing into endothelial cells.

This research was conducted with four groups of immunodeficient mice in which human prostate cancer cells had been implanted. Each group received a different treatment: a control agent (no drug); a chemotherapy agent (docetaxel) only; an anti-angiogenic drug (thalidomide) alone; and both chemotherapy and the anti-angiogenic drugs.

Circulating endothelial cell (CEC) levels were measured before all four groups were treated and at specific times during the study. In the group receiving only chemotherapy, blood levels of dead CECs soon increased, up to 2.6 fold. In the animals treated with the two drugs, CEC death was higher – up to 4.3 fold -- suggesting that the anti-angiogenic agent may have enhanced chemotherapy’s ability to kill the tumor vascular endothelial cells.

Tests conducted later in the study revealed that treatment with the anti-angiogenic drug alone reduced the level of viable CECs by 18 percent, while treatment with only chemotherapy decreased it by 61 percent. The combination of both drugs further diminished the blood levels of viable CECs by 75 percent, indicating that the anti-angiogenic drug may have inhibited the immature endothelial cells in the bone marrow from reproducing and differentiating into adult cells.

Li is continuing her research on CECs in cancer. “We are in the process of testing whether this biomarker is exclusive for anti-angiogenic therapy,” she added. “Hopefully, the knowledge we learn pre-clinically will be translated into a useful biomarker for 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 more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

Test Helps Identify Patients with Breast Cancer Who Will Likely Benefit from Chemotherapy, and Those Who Won’t

registration@aacr.org () — Fri, 15 Sep 2006 12:00:00 GMT

CHICAGO -- A test that measures the amounts of two members of the same protein family - one of which appears to act as an oncogene, and the other as a tumor suppressor - helps identify patients with breast cancer who will likely benefit from chemotherapy and those who won’t, according to researchers.

The test, known as OncoPlan™, is already commercially available, and studies have shown that it can predict the aggressiveness of the patient’s tumor and the relative risk of disease recurrence following surgery in breast, colon and gastric cancers. Now, researchers in the U.S. and Canada have studied whether it also can help identify breast cancer patients who would benefit most from chemotherapy.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

OncoPlan measures two forms of Shc protein, which are known to drive the formation of protein complexes involved in signal transduction pathways and have been found to be involved in many of the pathways important to development of aggressive cancer. These two forms have a “push pull” relationship with each other: tyrosine-phosphorylated (PY)-Shc helps drive these dangerous cell pathways, but p66 Shc, after initial stimulation, works to inhibit the very growth pathway the other Shc proteins promote.

“This may be one mechanism whereby normal cells prevent runaway growth,” said the study’s lead author, A. Raymond Frackelton, Jr., Ph.D., a Brown University associate professor, staff scientist at Roger Williams Medical Center and Vice President of Research at Catalyst Oncology, which is marketing OncoPlan. “Perhaps more importantly, aggressive cancer cells must endure oxidative stress—stress that in normal cells triggers p66 Shc to cause cellular suicide,” he said. “Tumor cells, then, may have both growth and survival advantages if p66 Shc levels are low.”

Chemotherapy-mediated killing of tumor cells, however, does not require p66 Shc, Frackelton said, suggesting that patients whose tumor cells have low p66 Shc might respond well to chemotherapy. To test this idea, the researchers looked at the Shc proteins in tumors from 2,380 women from British Columbia who were diagnosed with invasive breast cancer, 717 of whom received chemotherapy as part of their initial treatment.

They found that, indeed, patients who had low levels of p66 Shc and did not receive chemotherapy had very poor outcomes. If similar patients received chemotherapy, however, their chances of relapsing and dying from their disease were reduced by two-fold or more, said Frackelton. Conversely, women with high levels of p66 Shc had a much higher likelihood of surviving their disease, but appeared to derive no benefit from chemotherapy, he said.

Possible additional associations between PY-Shc and chemotherapy benefit has not yet been fully explored, Frackelton said. “But even at this point, the results are very exciting because, with further validation in clinical trials, OncoPlan, which is already being used to predict disease aggressiveness, will help to ensure that individual patients receive the most beneficial therapies,” 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 more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

Abnormal Overexpression of p53 is a Predictive Molecular Biomarker of Advexin Efficacy in Recurrent Squamous Cell Carcinoma of the Head and Neck

registration@aacr.org () — Thu, 14 Sep 2006 12:00:00 GMT

CHICAGO -- A common laboratory test that predicted poor outcome from traditional radiation and chemotherapy treatment for head and neck cancers now has been found to predict a good prognosis with treatment of p53 tumor suppressor gene therapy - making it potentially the first predictive biomarker test for a gene-based drug.

Researchers at Introgen Therapeutics, Inc., in Austin, Texas, found that patients with advanced squamous cell carcinoma of the head and neck cancer (SCCHN) whose pre-treatment tumor samples over-expressed p53 protein were significantly more likely to respond to Advexin therapy than those whose tumor showed little p53 protein. Advexin is a gene based drug, injected directly into tumors, which uses an adenoviral vector to deliver the wild type p53 gene to tumor cells.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

“Not only do we now have a way to predict if the gene therapy is likely to succeed, those patients for which it does work are the hardest patients to treat,” said Laura L. Licato, Ph.D., associate director for Clinical Research at Introgen. “Accumulation of p53 has corresponded with a poor response to traditional therapies, as well as lower survival and a shorter time to disease progression.”

“Selecting those who have the best chance of responding to p53 tumor suppressor gene therapy also helps perfect clinical trial testing,” Licato said.

The researchers specifically found, in a subset of patients from phase II clinical trials, that 73 percent of patients with p53-positive tumors responded to the therapy, compared to a 14 percent response in patients with tumors that were p53-negative. Median survival also increased to 11 months for p53-positive patients, compared to 3 months for those with p53-negative tumors.

Head and neck cancer is the fifth most common cancer worldwide. Each year approximately 40,000 Americans are diagnosed with head and neck cancer, and about 11,000 patients will die.

Many cancers have a dysfunction in the p53 pathway that regulates the cell cycle, helping to protect against cancer formation, but researchers estimate that more than 50 percent of head and neck tumors over-express p53 protein. That suggests a defect in protein regulation or that the p53 gene is mutated, incapable of producing effective protein. Tumors that are p53 negative likely have a working p53 gene and protein pathway, as normal p53 levels in cells are typically low.

Advexin is farthest along in federal Food and Drug Administration (FDA) review of any experimental gene therapy, according to Introgen, and has been granted fast track designation for an application of use in head and neck cancer. Results from two phase II clinical trials involving more than 160 SCCHN patients have found that 18 percent of patients treated with Advexin achieved local regional disease control. Two other phase III trials in the disease are underway. According to Introgen’s published research, Advexin has also achieved 100 percent response when combined with chemotherapy to treat locally advanced breast cancer, and a 69 percent response when used with radiation to treat non-small cell lung 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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

Single Genetic Assay Could Help Physicians Decide When to Switch Patients from Gleevec to Sutent

registration@aacr.org () — Thu, 14 Sep 2006 12:00:00 GMT

CHICAGO -- Researchers have found that the same gene mutation responsible for a tepid response to Gleevec (imatinib) in treatment of gastrointestinal stromal tumors (GIST), bestows benefit when a newer targeted therapy, Sutent (sunitinib), is used.

They also discovered that a different GIST tumor mutation predicts the opposite - a better response to Gleevec than to Sutent.

This means, the researchers say, that a single genetic assay could potentially help physicians decide when to switch patients from Gleevec, the first-line treatment, to therapy with Sutent, which the FDA approved for second-line use for this cancer in January 2006.

Results were presented at the first meeting on the Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

“This is a story about personalized medicine,” said the lead researcher, Michael C. Heinrich, M.D., professor of medicine at Oregon Health and Science University. “Treatment isn’t one-size-fits-all anymore. We can individualize therapy based on the types of mutations found in tumor cells.

“In the case of GIST, we now understand more about how the mutational status of a patient’s tumor predicts response to different targeted therapies.”

Gleevec revolutionized the care of GIST, a rare cancer resistant to chemotherapy when advanced. Gleevec blocks the abnormal tyrosine kinase enzyme that plays a role in both chronic myeloid leukemia (CML) and in GIST, for which the drug was approved for use in 2001, and 2002, respectively.

But not all patients respond equally well to Gleevec, and many become resistant. Follow-up studies have found that the various mutations present on the tyrosine kinase enzyme can predict the degree of Gleevec benefit, Heinrich said. For example, 85 percent of GIST patients have a mutation in their tumor cell’s c-kit gene, which encodes a tyrosine kinase receptor, and the two-thirds of those patients whose mutation occurs in exon 11 of the molecule have the longest average response to Gleevec. But these tumors often mutate again, conferring resistance to Gleevec. The 10-15 percent of patients with a mutation in exon 9 don’t respond as well to the drug, but are less likely to mutate again, and those with no mutations show the least benefit, he said.

Sutent, a more potent tyrosine kinase inhibitor with a wider range of action, demonstrated a survival turnaround for Gleevec-resistant patients in recent studies, so Heinrich and his research team looked to see whether c-kit exon position also predicted response to Sutent.

They examined primary and secondary mutations in tumor samples from 74 patients, and found “a striking relationship,” Heinrich said. “Patients with tumors that are wild type or have an exon 9 mutation have a longer survival when treated with Sutent than do patients with an exon 11 mutation.” he said. “We are trying to figure out why that is so, but we also found that 62 percent of tumors with exon 11 mutations mutated again, and that some of these secondary mutations respond to Sutent while others don’t.

“These results suggest that patients with exon 11 mutations should stay on Gleevec for a longer period of time before switching to Sutent, Heinrich said, “and that the switch to Sutent could occur earlier when treating cancers with exon 9 mutations or no mutations.”

# # # #

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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

tNOX Serves as a Serum Marker for Detection and Monitoring of Disease

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- A team of researchers at Purdue University has found a protein in the blood that may prove to be more reliable than the standard prostate specific antigen (PSA) test in measuring the extent of prostate cancer.

According to D. James Morre, Ph.D., distinguished professor of medicinal chemistry at Purdue, the protein -- called tNOX -- is a member of a family of proteins that are involved in cell growth.

Normal cells express the NOX enzyme only when they are dividing in response to growth hormone signals. In contrast, cancer cells have gained the ability to express NOX activity at all times. This overactive form of NOX, known as tNOX – for tumor-associated NOX – has long been assumed to be vital for the growth of cancer cells, because drugs that inhibit tNOX activity also block tumor cell growth in culture.

Morre’s group -- in collaboration with colleagues at NOX Technologies in West Lafayette, Indiana, and Marshall Edwards Inc. in New York -- wanted to determine if the tNOX protein could be used to monitor disease progression in prostate cancer. That is, could tNOX serve as a biomarker for not only detecting the cancer, but also in gauging the amount of disease.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

Prostate cancer can be difficult to detect and track because of inaccuracies in current testing methods. The PSA test gives false-positive readings at least 20 percent of the time, resulting in unnecessary biopsies to confirm disease. The digital rectal exam in which a doctor physically checks the prostate is also plagued with reliability problems. At the same time, relying on changes in PSA levels to correlate with disease progression – whether with treatment or not – can be problematic.

In the study, Morre’s group collaborated with Marshall Edwards Inc., which was conducting a phase II clinical trial in Australia with an experimental drug called phenoxodiol in late-stage metastatic prostate cancer. Blood samples were taken prior to, midway, and at the end of the 12-week treatment, and analyzed for tNOX. They were compared to PSA levels in the blood that were taken at the same times.

Of 19 patients in the trial, nine -- who had prostate cancer that was continuing to grow based on PSA levels -- showed on average a 60 percent greater amount of circulating tNOX protein compared to those patients who had stable (7) or falling (3) PSA levels.

“It’s the first demonstration that we have – assuming that PSA levels indicate major tumor burden in some fashion – that tNOX levels also reflect tumor burden during and after therapy for prostate cancer,” said Morre. “That is, the more prostate cancer present as evidenced by PSA levels, the more tNOX protein that is present.”

He said that tNOX would probably find greater use in estimating the amount of cancer, rather than in detection, and could be another useful marker for monitoring an individual’s response to therapy.

While rising PSA levels are usually associated with worsening disease, PSA scores can be erratic, he said. Individuals with substantial disease can still have a low PSA score, and those with moderate or even non-existent disease can show a high PSA.

“We think our marker may be more closely aligned to tumor burden than PSA,” Morre said. “It looks like it stands a better chance of being proportional to tumor burden and may be more reliable. It seems to be more uniform in terms of disease severity.”

In future work, the researchers hope to conduct more extensive clinical trials to try to link tNOX and PSA levels as estimates of tumor burden and to monitor responses to therapy of patients with late-stage metastatic 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 more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

A tNOX-based Protocol for Early Detection of Lung Cancer in Smokers and Non-Smokers

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- Lung cancer is a formidable disease. While it is one of the most preventable cancers, with the vast majority of 160,000 annual deaths in the United States due to smoking, it is invariably difficult to find early when it is most amenable to treatment. As a result, it remains the top cancer killer in the nation.

But a new test for the early detection of lung cancer that involves measuring levels of a certain protein may provide hope for thousands of smokers worldwide. While the findings are preliminary and involve a small group of subjects, the researchers see their early results as extremely promising.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

A team led by Dorothy M. Morre, Ph.D., professor of foods and nutrition at Purdue University in West Lafayette, Indiana, and D. James Morre, Ph.D., distinguished professor of medicinal chemistry at Purdue, wanted to come up with a robust lung cancer screening procedure for people who smoke.

“We’d like to have a means of detecting lung cancer early in individuals who smoke with a low incidence of false positives,” Dorothy Morre said. “There’s apparently no good method of finding this and there is a lot of interest at the National Cancer Institute in developing such a protocol.”

The Morres -- along with colleagues at Purdue, NOX Technologies, Inc., also in West Lafayette, and at Mount Sinai Medical Center in New York -- focused their efforts on a protein called tNOX, a member of a family of proteins that are involved in cell growth. Normal cells express the NOX enzyme only when they are dividing in response to growth hormone signals. In contrast, cancer cells have gained the ability to express NOX activity at all times. This overactive form of NOX, known as tNOX – for tumor-associated NOX – has long been assumed to be vital for the growth of cancer cells, because drugs that inhibit tNOX activity also block tumor cell growth in culture.

The researchers compared four different protocols to determine levels of tNOX in the blood of 421 volunteer subjects, including 104 patients with lung cancer, 175 smokers who had not been diagnosed with lung cancer, 117 randomly selected outpatients and 25 healthy individuals.

Two of the protocols used rapid high-throughput screening techniques and gave a low incidence of false-positive diagnoses of lung cancer. In contrast, the researchers employed a technique using two different antibodies that they created against the tNOX protein, which they found gave a definitive indication of lung cancer.

“In healthy individuals, we have 0 out of 25 false positives,” noted D. James Morre. “In lung cancers, 103 of the 104 patients were positive for tNOX. In smokers older than 40 years of age, 12 percent were positive, which is about the normal incidence picked up with high resolution tomography.”

The researchers envision the tNOX test as serving as a screening tool for the early detection of lung cancer. Those who test positive would then be followed up with a medical examination and further tests, ostensibly including high resolution CT.

According to D. James Morre, current approaches to diagnosing lung cancer are costly and time consuming. “Our findings would provide a simple blood test that would indicate whether or not additional testing would be required,” he said. “We could screen very large smoker populations and eliminate perhaps 90 percent of them, while encouraging the other 10 percent to go on to the next stage of testing.

“This test is structured with the antibody we’re using to be specific for lung cancer in one form or another,” Dorothy Morre added. “It’s a specific diagnosis and it also distinguishes between non-small and small cell lung cancer.”

The scientists are already doing similar studies in colon, ovarian, prostate and breast cancers as well. They are planning three collaborative studies in which they will correlate tNOX antibody test results with medical evidence such as high resolution CT, physician examinations of patients – standard procedures for detecting early stage lung 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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

REG1A and Its Receptor EXTL3 Are Prognostic Markers for Colorectal Cancer Recurrence

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- Two genes, known as REG1A and EXTL3, are overexpressed in colorectal tumors of patients who are at high risk of recurrence, according to a new study from the Max Delbrueck Center in Berlin, Germany.

In this study, REG1A expression was also significantly higher in surgical biopsies taken from pre-cancerous colon polyps, or adenomas.

“The findings suggest that the two genes are significant prognostic markers and may eventually help in making decisions about management of colorectal adenomas and tumors,” said principal investigator Wolfgang Kemmner, Ph.D., who is Surgical Oncology Research Group Leader at the Max Delbrueck Center.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

The researchers analyzed tumor and normal tissue from 75 colorectal cancer patients who had undergone surgery but not yet received any other treatment. They discovered that REG1A (Regenerating Islet-Derived 1 Alpha) was overexpressed in tumor specimens compared to normal tissue. In general, its level of expression correlated with the length of time before the disease recurred--as REG1A expression levels increased, disease-free survival decreased.

Patients with higher expression levels also tended to have lower disease-specific survival, meaning less time before they died from their disease. In addition, REG1A expression was significantly higher in tumors with peritoneal carcinomatosis, a type of advanced cancer in which many small tumors develop on the abdominal cavity and linings.

The other gene, EXTL3 (Exostoses (Multiple)-Like 3), which was examined in samples of 56 patients, also tended to be upregulated in peritoneal carcinomatosis and was a significant predictor of patient outcome. EXTL3 encodes the receptor to which the REG1A protein binds.

Turning to precancerous adenomas, the researchers compared adenoma tissue from 22 patients to colorectal mucosal tissue from 31 healthy individuals. REG1A expression was significantly higher in the adenomas.

Taken together, the findings raise the possibility that the genes could help guide decisions regarding both treatment and prevention of the disease.

“On the one hand, determining REG1A and EXTL3 expression levels could eventually help show which surgical patients are at high risk for recurrence and thus need more aggressive treatment,” Kemmner said. “In addition, REG1A expression may serve in molecular diagnosis of very early tumors not yet apparent from conventional histopathology.”

# # # #

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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

Molecular Markers Signal Early Metastases from Ocular Melanoma

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- Patients with melanoma of the eye are at risk for liver metastases, which are often not detected until they have turned into large, lethal tumors. Now researchers have found molecular markers, including changes in a particular chromosome, that flag the presence of small metastases before they reach life-threatening size.

In a second important finding, the researchers showed that a common procedure, called fine needle biopsy, could be used to accurately detect these molecular signatures.

“The results show that we can pinpoint these molecular markers in the small amount of RNA and DNA obtained from fine needle biopsy,” said principal investigator J. William Harbour, M.D., Associate Professor of Ophthalmology/Cell Biology/Medicine at Washington University School of Medicine in St. Louis.

“This means that testing for the markers is clinically feasible and could be used routinely to identify patients with ocular melanoma who are at high risk for metastasis.”

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

In prior studies, Dr. Harbour and his colleagues found that a particular molecular signature—the pattern of expression, or activation, of a group of 3 to 10 genes—was an accurate predictor of metastasis. On the basis of this gene expression pattern, patients with ocular melanoma can now be divided into two groups: Those with a class 1 molecular signature have little risk of metastasis while those with a class 2 signature have a high risk.

In this study, the St. Louis researchers first tested whether the minute quantities of RNA obtained from fine needle biopsies were adequate to detect the class 1 and class 2 signatures. The results were positive. The signatures obtained from the fine needle biopsies corresponded to signatures obtained through conventional biopsies and to those found in the earlier studies.

Secondly, the researchers found that DNA from the fine needle biopsies included another biomarker: On chromosome 8, the loss of DNA in the p region correlated with time to metastasis. Among patients with 8p loss, the median time to metastasis was 25.8 months while for those without 8p loss, it was 37.4 months.

The authors conclude that RNA- and DNA-based testing of fine needle aspirates is clinically feasible and accurately predicts metastatic risk and time to metastasis in ocular melanoma.

The next step, Dr. Harbour said, is a larger, multicenter study in which cancer centers around the country will obtain fine needle aspirates from ocular melanoma patients and send them to Washington University for analysis. If this study confirms the usefulness of the procedure on a large scale, it could become routine practice.

Patients at high risk for metastasis could then opt for further, preventive treatment, including clinical trials of new targeted agents and immunotherapies, Dr. Harbour said.

“Because we can now identify high risk patients, we can design clinical trials specifically for this population,” he said. “And this could lead to more rapid development of new agents to prevent or slow down metastasis in ocular melanoma.”

# # # #

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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

New Technique Detects Early Metastasis of Breast Cancer

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- In the U.S., a novel technology soon may be available to detect the spread, or metastasis, of breast cancer earlier than now possible, according to research presented at the first international meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

Since secondary tumors, ignited by spreading malignant cells, and not the primary breast cancer tumor, are the primary cause of cancer death, early detection of metastatic spread is crucial to a woman’s prognosis.

It should enable the patient’s doctor to adjust the woman’s treatment so that it will target the spreading cancer early, said Winfried H. Albert, Ph.D., chief scientific officer of AdnaGen, the German biotech company that developed the technology.

Albert said that the company’s diagnostic tool, which is being evaluated in clinical studies at The University of Texas M. D. Anderson Cancer Center in Houston, can spot one malignant cell in a typical blood sample. A typical sample is 5 milliliters and contains over 2.5 x 10¹⁰ cells.

As a biomarker for breast cancer metastasis, cancer cells circulating in the blood system have not been easy to detect and analyze because they are a “needle in the haystack” among the millions of cells in the bloodstream.

However, Albert said that AdnaGen’s technology can detect the “needle” with a specificity of 97 percent (only three “false” positive results in tests of 100 seemingly healthy people).

“Metastasis usually is detected by costly, cumbersome physical methods like computer tomography (CT),” added Albert. “We have seen cases, where our test was positive, when there was still no clinical evidence. But at a careful second look through a CT scan, small metastatic lesions have been detected.”

To produce its diagnostic tool, AdnaGen links an antibody-mix to magnetic beads. This antibody-mix is tailored to home in on specific molecular features, or antigens, of the respective cancer cells.

When exposed to a blood sample, the magnetic antibody-beads capture tumor cells possessing the specified antigens. A magnetic particle concentrator then removes the tumor cells labeled with the magnetic beads, and the cells are then analyzed to identify several gene products, including potential molecular targets for a specific drug.

Using this technology, AdnaGen discovered that the genetic signatures of the breast cancer and its metastases may differ, with the circulating tumor cells reflecting the gene expression profile of the metastases.

When a metastases has been diagnosed, treatment “usually has been chosen according to the features of the primary tumor, neglecting the fact that metastases can differ considerably from them,” Albert noted.

AdnaGen, which is marketing its breast cancer assay (as well as assays for colon and prostate cancer) in Europe, is awaiting the results of a clinical trial before applying for FDA approval to make the test available in the U.S.

# # #

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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

Sensitive and Specific Biomarker for Early Detection of Prostate Cancer Identified

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- Scientists at a Maryland-based pharmaceutical company have preliminary evidence showing that a protein in the blood may prove to be a biomarker that is more sensitive and specific than current methods of early detection for prostate cancer.

If they’re right, the protein – an enzyme called human aspartyl (asparaginyl) beta-hydroxylase, or HAAH – could ultimately help reduce the number of unnecessary biopsies for prostate cancer and may identify cancer at an earlier stage when treatment would have a higher likelihood of success.

Prostate cancer is expected to account for more than 234,000 new cases and about 27,000 deaths in the United States in 2006. The American Cancer Society recommends that all men over 50 be screened annually with two standard tests: the prostate specific antigen, or PSA, which measures a protein in the blood, and the digital rectal exam, or DRE, which entails a physical exam to the prostate.

Yet the PSA and DRE can be inexact and, at times, not specific or sensitive to cancer. High PSA levels are found in both cancerous and healthy tissue, particularly in benign prostate disease, resulting in significant numbers of false positive cases. The DRE, based on physician touch and skill, relies on subjective judgment. As a result, a man who has prostate cancer can have both a normal PSA and DRE. Conversely, an individual with a high PSA and an abnormal DRE could be cancer-free.

“There is a great need for a test that increases the sensitivity and specificity of those two other tests for prostate cancer,” said Stephen Keith, M.D., M.S.P.H., president and chief operating officer of Panacea Pharmaceuticals, Inc., Gaithersburg, MD.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

“Currently, if an individual has a high PSA and positive DRE, the recommendation is that he has a biopsy of the prostate, and more often than not – by some estimates, as much as 80 percent of the time – there will not be evidence of cancer,” Dr. Keith said.

Yet, biopsies can be painful, expensive and difficult to perform, and may cause a high number of infections, noted Hossein Ghanbari, Ph.D., chief executive officer and chief scientific officer at Panacea.

According to Ghanbari, HAAH is overexpressed in at least 20 types of cancer tested to date, including liver, breast, ovarian, colon, esophageal, and prostate. It has been shown to be involved in tumor growth, invasiveness and cancer spread.

The researchers previously examined tissue from more than 20 different cancer types and compared them to more than 1,000 normal tissue types. Using immunohistochemistry techniques, they found that more than 99 percent of cancers were positive for HAAH. None of the normal issue samples were positive.

To find a more accurate way to detect prostate cancer, Ghanbari and his co-workers at Panacea developed a test in which they could detect HAAH in blood serum.

In the current work, Ghanbari and his co-workers compared HAAH levels in the blood of 16 individuals with prostate cancer to 23 healthy individuals. Those with prostate cancer showed high HAAH levels, whereas none of the normal control individuals did.

“We’ve learned that HAAH is generally detected in prostate cancer and not in normal prostate tissue, in addition to a number of other cancers,” he said.

The scientists foresee the HAAH test used in conjunction with DRE and PSA testing. “We hope our HAAH blood test combined with PSA and DRE will increase the sensitivity and specificity of screening for prostate cancer,” said Keith. “Those without cancer can avoid unnecessary biopsies through the use of all three screening tests.”

“Having a positive DRE and high PSA, the HAAH would put the final stamp of approval,” Ghanbari said.

Panacea scientists are planning clinical trials with prostate tissue samples from 800 patients, including 400 men with prostate cancer and 400 healthy individuals.

“The goal is to be able to take someone with increasing PSA numbers and a positive DRE, measure the HAAH level and look at biopsy results,” Ghanbari said, “and be confident that HAAH provides the additional benefit in terms of specificity and sensitivity. The addition of HAAH should improve the prediction of who will have positive biopsy results for prostate 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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

High-throughput Oncogene Mutation Detection in Human Cancers by Mass Spectrometry-based Genotyping

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- Researchers have devised a new method to detect a spectrum of known gene mutations in a variety of cancer genes that they say is both sensitive and cost-effective. They say that if validated, this method of genotyping might ultimately be used in “real time” to match patients to available targeted therapies.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

The technique, developed at the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT, may also offer aid in the testing and development of tailored treatments, according to researcher Levi A. Garraway, M.D., Ph.D., an assistant professor in the Dana-Farber Department of Medical Oncology. “It may help clinical testing of new targeted therapies, because patients can, in principle, be screened in advance for activating mutations in the protein the agent is directed against,” he said.

It could also help eliminate a “significant bottleneck” in the development of drugs, which is the ability to test for multiple types of cancer genetic alterations simultaneously in the clinic. “Tests that use DNA sequencing to look for mutations in a single gene can cost a couple thousand dollars,” Dr. Garraway said. “We ran a whole panel of genes for about $60 each, and the price could drop below that with more updated methods.”

The method uses high-throughput mass spectrometry-based genotyping, which is a sensitive and accurate method to detect single nucleotide polymorphisms (SNPs) in DNA. But while this tool is mostly used to understand how single letter (or nucleotide) changes in genes might correlate with disease risk in normal individuals, the researchers adapted it to look for known point mutations in genes that make them oncogenic.
They chose oncogenes known to contain “dominant activating mutations in many tumor types. In a lot of cases, the entire biology of the tumor is conditioned around such mutations, so if you eliminate the oncogene, the tumor shrinks,” Dr. Garraway said. Examples include the c-kit tyrosine kinase that drives development of gastrointestinal stromal tumors (GISTs), and certain EGFR mutations that are responsible for one form of lung cancer. These cancers can be treated with the targeted therapies Gleevec and Tarceva, respectively, which shut down the affected oncogenes.

The test involves taking a sample of fresh or frozen tumor, amplifying its DNA, and then searching for 250 known mutations in 17 oncogenes. (These include members of the ras, EGFR, pi3 and c-kit kinase families, among others.) To check performance of the genotyping, the research team tested over 1,000 tumors, representing 15 different cancer types, and then independently verified over half of the mutations they identified using traditional DNA sequencing or other methods. They found that over 92 percent of mutations identified by the mass spectrometry method were validated in this manner, and believe that much of the difference is due not to the mass spectrometry method but to limitations of the laborious sequencing test “which is not always sensitive in tumor specimens,” Dr. Garraway said.

He added that the mass spectrometry test offers information that is distinct from the cancer microarray gene expression tests now being developed. “Those tests depend on gene expression while this one looks directly at problems in the genome,” Dr. Garraway 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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

Novel Biomarker for Prediction of Survival in Colorectal Carcinomas Revealed

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- Levels of a protein called thymidylate synthase (TS) within two separate compartments of a tumor cell—the nucleus and the cytoplasm—may be critical markers predicting survival in colorectal cancer, according to a study at Yale University School of Medicine.

The study revealed two different and independent predictors of survival in colorectal cancer. One was TS levels in the nucleus—the higher the levels, the lower the survival time; and one was the ratio of TS levels in the nucleus to levels in the cytoplasm—the higher the ratio, the lower the survival time.

“TS levels have been known as a marker for decreased survival and response to therapy, but this is the first study to show that the relationship between nuclear and cytoplasmic levels of TS can predict survival,” said first author Mark D. Gustavson, Ph.D., a postdoctoral fellow in Yale’s Department of Pathology.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

To determine subcellular TS levels, Gustavson and his colleagues used AQUA™, a system that combines fluorescence-based imaging with automated microscopy and high-throughput tissue microarray technologies. Developed at Yale and licensed to HistoRx, AQUA can measure protein concentrations within specific cells and cellular compartments in a highly reproducible and unbiased manner, Gustavson said.

Working with tissue samples from 518 colorectal cancer patients diagnosed between 1970 and 1981, the researchers found that just 51 percent of patients with high TS levels in the nucleus survived for five years compared to 71 percent of those with lower levels. The difference was highly statistically significant. TS levels in the cytoplasm were also higher in patients with lower survival times, though they were not as strong a predictor of survival as TS levels in the nucleus.

The researchers next looked at the ratio between TS levels in the nucleus and in the cytoplasm and discovered that a high ratio predicted decreased survival. Moreover, the cytoplasmic-to-nuclear ratio appeared to be an independent marker, not correlated with high nuclear levels. Among patients with a high ratio, more than half (55 percent) did not have high nuclear levels.

“The ratio identifies a group of patients with worse prognosis that would otherwise be missed,” Gustavson said.

After taking into account other predictors of survival, including stage, age at diagnosis, gender, and race, both nuclear TS levels and the cytoplasm-to-nucleus ratio emerged as independent predictors of survival.

“This is a new potential biomarker for predicting survival in patients with colorectal cancer,” said Gustavson. Up to now, standard immunohistochemistry has been used to measure only absolute levels of TS. However, this study shows that TS expression levels within different subcellular compartments and their relationships should also be considered, he said.

The researchers also note that the markers may help in predicting response to therapy with 5-FU, one of the standard chemotherapy drugs used in colorectal cancer, since TS levels have been shown to be critical in modulating response to the drug. Currently a retrospective study is examining whether these two biomarkers can predict response to 5-FU.

# # # #

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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

Biomarkers of Response to VEGF Pathway-targeted Therapy Discovered for Renal Cell Carcinoma

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

CHICAGO -- Angiogenesis inhibitors can be far more effective in treating metastatic clear cell renal cell cancer (RCC) - an aggressive form of the most common kind of kidney cancer that is also rich in blood supply - than traditional treatments, according to accumulating evidence. They can prolong life in about a third of patients, but researchers have not been able to identify the responding patients, prior to treatment.

Now, a research team from the University of California, San Francisco (UCSF) and the Cleveland Clinic, has found that patients whose tumors produce greater amounts of vascular endothelial growth factor (VEGF) and its receptor benefit most from these targeted treatments, because these proteins are the “targets” they are designed to go after.

“The more VEGF and VEGF receptor a patient’s tumor has, the better these treatments seem to work,” said the study’s lead author, Erich B. Jaeger, Ph.D., a postdoctoral researcher at the UCSF Comprehensive Cancer Center. “This is very exciting because, if validated, a fairly simple test could help oncologists direct these new treatments to patients who can benefit most from them.”

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

Clear cells RCCs often accumulate VEGF and other angiogenesis-related proteins due to mutation in the Von Hippel-Lindau (VHL) tumor suppressor gene. This gene was identified as the cause of the rare and inherited Von Hippel-Lindau disease, which is characterized by frequent development of clear cell renal tumors.

About half of non-inherited clear cell renal cell cancer is believed to result from mutations in the VHL gene, Jaeger said. The mutations prevent proper degradation of specific VHL target proteins, which leads to over-expression of VEGF and other proteins associated with angiogenesis, he said. These proteins cause the tumor to become highly vascular, establishing a solid blood supply to feed the cancer. When functioning normally, VHL helps regulate the production of those proteins that might otherwise contribute to tumorigenesis.

But not all VHL mutations are alike, Jaeger says. Some cause substantial changes in the protein it encodes, leading to accumulation of VEGF, and others cause less functional difference.

In this study, the research team examined 43 tumor samples taken before patients were slated to receive angiogenesis inhibitors, and they found that 25 contained VHL mutations. Of these, 15 had mutations that led to severe disruption of the normal structure of the VHL protein.

They then correlated response to the drug with the level of VEGF and its receptor in the samples, and found that “patients who had the highest levels of expression of VEGF receptor had the best response to therapy,” Jaeger said. These patients experienced nearly a doubling in time to progression, gaining about six months, he said. “Because high levels of these proteins help drive the growth of tumors, it makes sense that if they are targeted and eliminated, the tumors don’t progress as fast.”

The researchers are preparing to test their mutational analyses on a set of renal tumor samples taken from 700 patients who were treated with Avastin, an angiogenesis inhibitor initially approved to treat advanced colon cancer. They also plan to improve the test by adding certain common mutations involving tumor suppressor genes, and the ability to look for these same mutations in paraffin-embedded tumors, which is how most samples are now prepared.

# # # #

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 60 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:

Warren R. Froelich
215/440-9300, ext. 198
In Chicago 9/12-9/15/06:
312-239-4757 ext-4757
froelich@aacr.org

Raloxifene Reduces Breast Cancer Risk in Postmenopausal Women at All Risk Levels

registration@aacr.org () — Wed, 13 Sep 2006 12:00:00 GMT

PHILADELPHIA − Raloxifene protects postmenopausal women from developing invasive breast cancer whether they are at high or low risk of developing the disease, according to a new study.

The study, published in the September 1 issue of Clinical Cancer Research, also revealed that the drug appears to reduce risk in women with a family history of breast cancer down to a similar level to women without affected relatives.

Compared with a placebo drug, the study found that use of raloxifene was associated with a 58 percent reduction in breast cancer risk in women without a family history of the disease, and an 89 percent reduction in risk for women with a family history of breast cancer.

But the researchers say they cannot explain why protection seems greatest in women who may be genetically predisposed to develop the disease.

“We don’t know what to make of this observation,” said Marc E. Lippman, M.D., professor in the Department of Internal Medicine at the University of Michigan and the study’s lead author. “It could be due to chance, or there may be other factors at work that we don’t know about.”

“But our bottom-line analysis as to why raloxifene universally reduces the risk of developing invasive cancer in women without a family history is that it interferes with the duration and concentration of estrogen, which acts as a tumor promoter in the majority of breast cancers,” said Dr. Lippman.

The research team conducted a new analysis of the first large study of raloxifene, which tested the ability of the drug to prevent vertebral fractures in 7,705 postmenopausal women diagnosed with osteoporosis. The secondary endpoint of this multi-center, double-blind trial, known as MORE (Multiple Outcomes of Raloxifene Evaluation) was the drug’s effect on breast cancer development; results, announced in 1999, demonstrated a 72 percent reduction in invasive breast cancer incidence after four years of raloxifene treatment, compared to use of a placebo.

The MORE trial was then extended four years to further evaluate the effect of raloxifene on breast cancer incidence in 4,011 of the original participants. Results of this trial, known as CORE (Continuing Outcomes Relevant to Evista), showed that eight years of raloxifene treatment was associated with a 66 percent decrease in invasive breast cancer incidence.

The current study was undertaken to assess the effect of raloxifene on level of breast cancer risk (higher versus lower) using data from both MORE and CORE.

Women at higher risk for breast cancer are generally older and have a greater lifetime exposure to estrogen, and the researchers found that this association held true in the reanalysis. But they also found that raloxifene reduced breast cancer risk in both women at lower and those at higher breast cancer risk, except for those women who had measurably low levels of estradiol, the major estrogen hormone in humans.

“In each variable commonly associated with a higher risk for developing breast cancer − age older than 65, age at menopause, a body mass index greater than 25, higher estradiol levels, prior use of estrogen replacement and a family history of breast cancer − use of raloxifene reduced incidence of breast cancer when compared to a placebo drug,” Dr. Lippman said. “But it also reduced incidence in each of those variables that should have lowered risk, such as younger age, later menopause, etc., compared to use of a placebo drug.”

“We don’t define the lowest limit of risk, the point at which toxicity associated with use of raloxifene outweighs the benefits,” he said. Dr. Lippman stressed that he cannot comment on how raloxifene in this study measures up to tamoxifen use in general. He explains that although these findings come on the heels of the June publication of the 19,747-participant STAR trial, which evaluated tamoxifen against raloxifene in reducing breast cancer risk, no comparison can be made between the MORE, CORE and STAR clinical trials.

“These studies looked at two different groups of women,” Dr. Lippman said. “Women enrolled in STAR were at high risk for developing breast cancer, so presumably, they had higher levels of estrogen in general. Women who participated in MORE and CORE were older and had osteoporoses and it is assumed that these women generally have lower levels of estrogen, because that is a risk factor for development of the disorder.”

Raloxifene, also known by the trade name Evista, has not been approved by the federal Food and Drug Administration as an agent to prevent breast cancer development.

Co-authors of the study include investigators from the University of Pittsburgh, the Angeles Clinic and Research Institute, California Pacific Medical Center Research Institute, and Eli Lilly & Company, which manufactures raloxifene.

###

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 60 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:

Warren Froelich
215-440-9300
froelich@aacr.org

Vitamin D May Cut Pancreatic Cancer Risk by Nearly Half

registration@aacr.org () — Tue, 12 Sep 2006 12:00:00 GMT

PHILADELPHIA -- Consumption of Vitamin D tablets was found to cut the risk of pancreatic cancer nearly in half, according to a study led by researchers at Northwestern and Harvard universities.

The findings point to Vitamin D’s potential to prevent the disease, and is one of the first known studies to use a large-scale epidemiological survey to examine the relationship between the nutrient and cancer of the pancreas. The study, led by Halcyon Skinner, Ph.D., of Northwestern, appears in the September issue of Cancer Epidemiology Biomarkers & Prevention.

The study examined data from two large, long-term health surveys and found that taking the U.S. Recommended Daily Allowance of Vitamin D (400 IU/day) reduced the risk of pancreatic cancer by 43 percent. By comparison, those who consumed less than 150 IUs per day experienced a 22 percent reduced risk of cancer. Increased consumption of the vitamin beyond 400 IUs per day resulted in no significant increased benefit.

“Because there is no effective screening for pancreatic cancer, identifying controllable risk factors for the disease is essential for developing strategies that can prevent cancer,” said Skinner. “Vitamin D has shown strong potential for preventing and treating prostate cancer, and areas with greater sunlight exposure have lower incidence and mortality for prostate, breast, and colon cancers, leading us to investigate a role for Vitamin D in pancreatic cancer risk. Few studies have examined this association, and we did observe a reduced risk for pancreatic cancer with higher intake of Vitamin D.”

Skinner, currently in the Department of Population Health Sciences at the University of Wisconsin School of Medicine and Public Health, and his colleagues analyzed data from two long-term studies of health and diet practices, conducted at Harvard University. They looked at data on 46,771 men aged 40 to 75 years who took part in the Health Professionals Follow-up Study, and 75,427 women aged 38 to 65 years who participated in the Nurses’ Health Study. Between the two studies, they identified 365 cases of pancreatic cancer. The surveys are considered valuable for their prospective design, following health trends instead of looking at purely historical information, high follow-up rates and the ability to enable researchers like Skinner to incorporate data from two independent studies.

Pancreatic cancer is a rapidly fatal disease and the fourth-leading cause of death from cancer in the United States. This year, the American Cancer Society estimates that 32,000 new cases of cancer will be diagnosed. About the same number of people will die this year from the disease. It has no known cure, and surgical treatments are not often effective. Except for cigarette smoking, no environmental factors or dietary practices have been linked to the disease.

In addition to Vitamin D, the researchers also measured the association between pancreatic cancer and the intakes of calcium and retinol (Vitamin A). Calcium and retinol intakes showed no association with pancreatic cancer risk, although retinol is an antagonist of Vitamin D’s ability to influence mineral balances and bone integrity.

For that reason, further research is necessary to determine if Vitamin D ingestion from dietary sources, like eggs, liver and fatty fish or fortified dairy products, or through sun exposure might be preferable to multi-vitamin supplements, which contain retinol.

The potential benefits of vitamin D for pancreatic cancer were only recently established by other laboratory studies. Normal and cancerous pancreas tissue contain high levels of the enzyme that converts circulating 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D, the vitamin’s active form. Other studies have shown an anti-cell proliferation effect of 1,25-dihydroxyvitamin D, potentially inhibiting tumor cells.

“In concert with laboratory results suggesting anti-tumor effects of Vitamin D, our results point to a possible role for Vitamin D in the prevention and possible reduction in mortality of pancreatic cancer. Since no other environmental or dietary factor showed this risk relationship, more study of Vitamin D’s role is warranted,” Skinner said.

Skinner’s colleagues in the study include Dominique Michaud, Edward Giovannucci, Walter Willett and Graham Colditz of Harvard, and Charles Fuchs of the Dana-Farber 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 60 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.

Contact:
Warren Froelich
215-440-9300
froelich@aacr.org

American Association for Cancer Research Soliciting Nominees for Awards, Lectureships, Honoring Scientific Excellence

registration@aacr.org () — Fri, 01 Sep 2006 12:00:00 GMT

Nomination deadline: Monday, October 2, 2006

PHILADELPHIA — Continuing its long tradition of honoring outstanding achievement in cancer research, the American Association for Cancer Research currently is accepting nominations for its series of annual awards. Scientists advancing the understanding and eradication of cancer through basic research, clinical care, therapeutics and prevention are eligible. Winners will deliver a lecture during the AACR’s Centennial Year Annual Meeting, April 14-18, 2007, in Los Angeles, Calif.

Detailed information about each award and the nomination process are available on the AACR Website at www.aacr.org. The fields and corresponding awards represented are:

Basic cancer research:
AACR–G.H.A. Clowes Memorial Award, in honor of a founding member of the AACR and a research director at the Eli Lilly Company.

Improved clinical cancer care:
AACR–Richard and Hinda Rosenthal Foundation Award, which recognizes notable contributions on the part of medical practitioners aged 50 or younger who reside in the Americas, and 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.

Meritorious achievement by a young investigator:
AACR Award for Outstanding Achievement in Cancer Research, to give recognition to a young investigator (not more than 40 years of age) on the basis of meritorious achievement in cancer research.

Epidemiology, biomarkers and prevention:
AACR–American Cancer Society Award for Research Excellence in Cancer Epidemiology or Prevention, sponsored jointly by the AACR and the American Cancer Society.

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 give recognition to 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 click here. Inquiries regarding these awards should be directed to awards@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 60 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:
Sheri Ozard
215-440-9300, Ext. 114
ozard@aacr.org

THE PREMIER INTERNATIONAL MEETING: MOLECULAR DIAGNOSTICS IN CANCER THERAPEUTIC DEVELOPMENT

registration@aacr.org () — Tue, 29 Aug 2006 12:00:00 GMT

The American Association for Cancer Research to Host First-Ever Meeting on Potential Breakthroughs in Personalized Medicine

What:
The future of cancer treatment relies heavily on:

enhanced detection and classification of tumors;
accuracy to establish target validation and proof of concept;
improved patient selection to test therapeutic hypotheses most efficiently;
accuracy in dose and schedule determination; and
elucidation of mechanism of drug resistance developing
molecular risk models to identify high-risk cohorts.

This multidisciplinary conference will become the most important conference devoted to the latest developments in the integration of molecular diagnostics with cancer drug development. This meeting will offer unprecedented opportunities for the translation of basic science into new individualized therapeutic strategies.

This marks the first time that experts, including basic scientists, translational researchers, physician-scientists, clinical oncologists, cancer survivors, and behavioral researchers from academia, government, industry, and advocacy organizations will all come together to discuss the latest developments in molecular diagnostics.

Highlights include:

protocol for early detection of lung cancer in smokers and nonsmokers
serum marker for early detection and staging of prostate cancer
a novel biomarker for prediction of survival for colorectal carcinoma
molecular prediction of tumor to metastasis for ocular melanoma from needle aspiration
individualized therapy based on cancer cells and tumor grafts
oncogene detection in human cancers
p53 as a molecular marker for treatment efficacy in head and neck cancers
biomarkers of response to VEGF pathway-targeted therapy for renal cell carcinoma
correlation of mutation with imatinib resistance of GIST

When:
September 12-15, 2006

Where:
Hyatt Regency Chicago Hotel
Chicago, Ill.

Contact/Press Registration:
Yarissa Ortiz
215-440-9300
ortiz@aacr.org

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AACR Supports Appointment of John E. Niederhuber as Director of the National Cancer Institute

registration@aacr.org () — Fri, 18 Aug 2006 12:00:00 GMT

PHILADELPHIA – The American Association for Cancer Research (AACR), the world’s oldest and largest cancer research organization, congratulates Dr. John E. Niederhuber on his appointment as Director of the National Cancer Institute.

Dr. Niederhuber is a nationally recognized surgical oncologist with special clinical emphasis on gastrointestinal, hepatobiliary, and breast cancer. His pioneering work in hepatic artery infusion chemotherapy and implantable vascular access devices were major contributions to cancer care. He brings a long career of medical and administrative expertise to this position. Having served as a surgeon, laboratory and clinical researcher, cancer center director, and leader of several national cancer organizations, as well as in key senior positions at the National Cancer Institute, he has a unique perspective of the complexities of the cancer field from which to approach this new challenge. His experience will be vitally important in our efforts to further reduce cancer incidence and mortality.

“The AACR looks forward to working with Dr. Niederhuber to overcome the many challenges posed by this disease and to capitalize on the promise that three decades of investment have made available,” said Geoffrey Wahl, Ph.D., President of the American Association for Cancer Research.

Cancer research is advancing at a breathtaking pace. At this critical juncture in the evolution of cancer research, our ability to advance our understanding of the fundamental science of cancer, to make inroads in cancer prevention, and to speed the delivery of safe and effective therapies to patients has been severely constrained by inadequate funding. As a consequence, the NCI faces great challenges in meeting our mutual goal of further declines in cancer incidence, morbidity and mortality. “As Dr. Niederhuber stewards the NCI’s future investments in cancer research, the AACR will look to him for strong and creative leadership of the National Cancer Program to maintain the pace of current research while providing adequate and consistent funding to guarantee a place in cancer research for the bright young minds that will produce tomorrow’s discoveries,” said Dr. Wahl.

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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 60 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.

Contact:

Staci Vernick Goldberg
215-440-9300 ext. 145
goldberg@aacr.org

Cancer Stem Cells Spur Glioma Angiogenesis, Could Hold Key to Brain Tumor Therapy

registration@aacr.org () — Tue, 15 Aug 2006 12:00:00 GMT

PHILADELPHIA – Stem cell-like glioma cancer cells that share many characteristics with normal stem cells propel the lethal growth of brain cancers by promoting tumor blood vessel formation, and may hold the key to treating these deadly cancers, a research team reported in the August 15th issue of Cancer Research.

Led by Jeremy Rich, M.D., associate professor at the Preston Robert Tisch Brain Tumor Center at Duke University, the researchers found that a small subset of glioma cells expressed higher levels of a growth factor associated with cancer cell growth. They believe this subset could be a target for new therapies against these intractable brain tumors.

Gliomas are the most common type of brain tumor, making up about half of all diagnosed primary (or non-metastatic) brain tumors. About 17,000 people in the United States are diagnosed with a primary brain tumor each year. Patients with the most aggressive glioma, called glioblastoma, have an average life expectancy of less than one year despite advances in cancer treatment. To better treat cancer patients, laboratories like those of Rich are trying to better understand the causes of tumor growth so that gliomas can be targeted with new drugs.

“Malignant brain tumors are highly lethal, despite aggressive surgery, radiation, and chemotherapy,” said Dr. Rich. “We believe targeting the cancer stem cells of brain tumors may offer a novel therapy that will help to decrease the blood supply feeding a growing tumor, and therefore decrease or stop that tumor’s growth.”

Researchers from other laboratories recently determined that a small fraction of all the cells in a glioma have special characteristics similar to brain stem cells. These stem cell-like glioma cells form tumors when implanted in animals. As the ability to form new blood vessels (called angiogenesis) to supply blood carrying nutrients is critical in cancer growth, Dr. Rich’s team studied if the formation of tumors by stem cell-like glioma cells could be due to increased angiogenesis. Angiogenesis is often stimulated by a key growth factor called VEGF. Rich and colleagues found that stem cell-like glioma cells enhanced the angiogenesis of gliomas through increased levels of VEGF.

Using an antibody to mark the cancer stem cells in gliomas obtained from patient specimens, the Rich laboratory determined that between three-to-five percent of tumor cells were of the stem cell-like variety. They found that these stem cell-like glioma cancer cells expressed much higher levels of VEGF and formed more tumors with more blood vessels than glioma cells that did not have stem cell characteristics. Adding an antibody (bevacizumab, also known by the trade name Avastin) that blocks VEGF activity blocked new blood vessel formation and prevented tumor growth. The researchers suggest that the stem cell-like glioma cells, because of their support of angiogenesis, could hold an important target to suppressing the growth of brain cancer.

“VEGF antibodies may be effective as cancer therapies when combined with chemotherapy by improving delivery directly and specifically to stem cell-like tumor cells,” said Dr. Rich. “Targeting VEGF in this way would not kill cancer cells directly, but instead would block the actions of adjacent cells that support the growth of their blood supply.”

Dr. Rich’s lab studies the complex relationships between cell signaling pathways and the development of cancer, especially in the nervous system. The lab is investigating a number of molecular targets that contribute to cancer growth and malignancy.

“Too often, brain tumor patients have been told there is no hope. Our overall objective is to give brain tumor patients that hope, while we do not expect to achieve instant victories in the near future,” said Dr. Rich.

Dr. Rich’s colleagues in the study included Shideng Bao, Qiulian Wu, Sith Sathornsumetee, Yueling Hao, Zhizhong Li, Anita Hjelmeland, Qing Shi, Roger McLendon and Darell Bigner, all of Duke 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 more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 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. AACR’s 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:

Warren Froelich
215-440-9300 ext. 198
froelich@aacr.org

Early Exposure to Synthetic Estrogen Puts “DES daughters” at Higher Risk for Breast Cancer

registration@aacr.org () — Mon, 07 Aug 2006 12:00:00 GMT

PHILADELPHIA − So-called “DES daughters,” born to mothers who used the anti-miscarriage drug diethylstilbestrol during pregnancy, are at a substantially greater risk of developing breast cancer compared to women who were not exposed to the drug in utero.

Reporting in the August issue of the journal Cancer Epidemiology, Biomarkers & Prevention, a nationwide team of researchers found that DES daughters over age 40 had 1.9 times the risk of developing breast cancer, compared to unexposed women of the same age. They also found that the relative risk of developing the cancer was even greater in DES daughters over age 50, but say the number of older women in their study group is, as yet, too small for a firm statistical comparison.

“This is really unwelcome news because so many women worldwide were prenatally exposed to DES, and these women are just now approaching the age at which breast cancer becomes more common,” said the study’s lead author, Julie Palmer, Sc.D., professor of epidemiology at the Boston University School of Public Health. She said an estimated one to two million women in the U.S. were exposed to DES, which was frequently prescribed to women from the 1940s through 1960s to prevent miscarriages.

The ongoing study suggests that DES-exposed women are developing the typical range of breast cancers after age 40 at a faster rate than non-exposed women of the same ages. The researchers also found that the highest relative risk of developing breast cancer was observed in study participants from the cohorts with the highest cumulative doses of DES exposure. Because of the increased risk observed for DES daughters, the authors urge women who know they were exposed to DES to have regular screening mammograms, and to think twice about using supplemental female hormones.

“DES daughters often ask us about use of these hormones,” Palmer said. “It might be wise for exposed women to avoid such supplements. Use of hormone supplements is, in itself, an independent breast cancer risk factor, and women may choose not to compound their already increased risk.”

When DES, a synthetic estrogen, was developed in 1938, physicians believed that low levels of estrogen in pregnant women led to spontaneous abortions or premature deliveries. In 1953, a clinical trial indicated no benefit with regard to miscarriage prevention.

However, use continued in the U.S. until 1971 when researchers determined that DES greatly increased the risk of developing rare cancers of the vagina and cervix in DES daughters; the federal Food and Drug Administration subsequently banned use of the drug in pregnant women. Later research demonstrated that DES increased the risk of breast cancer development in the mothers who used it.

To see if DES daughters and sons were also at greater risk of cancer or other serious illnesses, in 1992 the National Cancer Institute (NCI) funded a long-term study that assembled all known “cohorts,” or groups of DES daughters that were already being studied (some since the 1970s), as well as a collection of unexposed women. This particular analysis included 4,817 exposed and 2,073 unexposed daughters, and, to date, 102 cases of invasive breast cancer have occurred in the combined group.

Factoring out other breast cancer risk variables such as the age when these women first gave birth, or their number of children, did not change DES daughters’ relative risk of developing breast cancer, Palmer said. She adds that the breast cancer cases “tracked the normal range” of breast cancer subtypes, so are expected to be neither more nor less lethal than is commonly seen. Only a few deaths have occurred in the combined group due to breast cancer, so survival statistics are not yet available, she said.

Scientifically, the study may be the first to provide direct evidence that prenatal exposure to excess estrogen may be a risk factor for development of breast cancer, Palmer said. “That theory has been around, but it has been difficult to study. The DES tragedy offers us a direct way to test the hypothesis,” she said.

Although researchers do not know how DES may increase breast cancer risk, Palmer said some scientists believe the excess estrogen increases the number of breast tissue stem cells available at birth − cells which could malignantly transform into cancer.

If true that excess estrogen in utero impacts breast cancer risk later in life, “there is a concern that other environmental factors that increases fetal exposure to estrogenic compounds may do the same thing,” Palmer said. “This study suggests that such environmental exposures may deserve more serious consideration.”

Editors Note: A PDF of the article is available. Please e-mail communications@aacr.org to request a copy.

# # # #

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 60 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. AACR's 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:
Warren Froelich
215-440-9300 ext. 198
froelich@aacr.org

Nominations Open for 2007 Pezcoller Foundation-AACR International Award for Cancer Research

registration@aacr.org () — Mon, 17 Jul 2006 12:00:00 GMT

Nomination Deadline: Friday, September 15, 2006

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 when their investigations are closely related in subject matter.

The Award consists of €75,000 and a commemorative plaque. The winner also will give an award lecture during the 98th AACR Annual Meeting in Los Angeles, Calif., April 14-18, 2007, and will officially receive the award of €75,000 at a May 2007 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 awards@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 60 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. AACR’s 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:
Sheri Ozard
215-440-9300 ext. 114
ozard@aacr.org

John T. Hunt, Ph.D. Elected Chairperson of AACR Working Group

registration@aacr.org () — Tue, 11 Jul 2006 12:00:00 GMT

PHILADELPHIA – John T. Hunt, Ph.D., executive director of oncology drug discovery at Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, N.J., has been voted Chairperson-elect of the Chemistry in Cancer Research Working Group of the American Association for Cancer Research (CICR/AACR). He will accede to the office of chairperson in April 2007 at the 98th Annual Meeting in Los Angeles, Calif.

The goal of CICR/AACR is to bring together distinguished chemists in cancer research and other cancer scientists in chemistry-related fields for ongoing discussion of the present status and future promise of this important discipline.

"I will work to further advance Working Group initiatives to increase the visibility and impact of chemists within AACR by broadening the membership of the Working Group and increasing involvement by young researchers,” said Hunt.

CICR/AACR began as a task force in 1999 and became a working group open for membership in 2006. There are currently more than 300 members. This was the inaugural election; previous chairs were appointed by AACR leadership.

Hunt, a founding member of CICR/AACR, currently serves on the editorial advisory board of the Journal of Medicinal Chemistry. He is the 2002 recipient of the Bristol-Myers Squibb Ondetti and Cushman Innovation Award.

For more information on CICR/AACR, please click here.

Editors Note: For a photograph of Hunt, please click 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 60 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:

Angela DeCicco
215-440-9300 ext. 104
decicco@aacr.org

Program Information:

Susan Waskey
215-440-9300 ext. 162
waskey@aacr.org

Higher Risk for Cervical Cancer Seen Among Women Infected with Multiple HPV Types

registration@aacr.org () — Mon, 10 Jul 2006 12:00:00 GMT

PHILADELPHIA – The risk for developing the tissue abnormalities, or lesions, that typically precede cervical cancer is much higher for women infected with multiple genotypes of the human papillomavirus (HPV) than previously reported, according to a study published in the July issue of Cancer Epidemiology, Biomarkers & Prevention.

Although doctors have known that the cervical tissue at the opening to the womb can harbor multiple HPV types, this study is the first to document that the risk for developing cervical cancer, the second most common form of cancer in women worldwide, is higher in females infected with multiple HPV types than those infected with just one HPV type.

In addition, the study’s findings provide baseline data for analyzing over time the impact of the newly approved vaccine, Gardasil, on the dynamics of HPV infection.

“Women who harbor multiple infections are at higher risk for cervical lesions than those ever infected with one type only and should be followed more closely,” said Eduardo L. Franco, Dr.PH., leader of the study and professor of epidemiology and oncology, and director, division of cancer epidemiology at McGill University.

Like previous studies on HPV in cervical cancer, the new research found that pre-cancerous abnormalities primarily occurred in women infected with HPV 16 and 18, the targets of Gardasil. The vaccine also will prevent infection by the HPV types 6 and 11 that are associated with genital warts, and thus is expected to prevent cervical cancer in thousands of women.

However, the vaccine will not protect against HPV 58, which the new study discovered to be far more oncogenic than others when found in co-infections with other HPV types. The study’s findings suggest HPV 58 should be one of the targets of the next generation of cervical cancer vaccines.

Indeed, the scientists discovered that the higher risk associated with HPV 58 in co-infections was similar to that conferred by HPV 16 in co-infections. Both HPV 58 and 16 “seemed particularly prone to increase risk” for pre-cancerous lesions in the cervix, said Helen Trottier, Ph.D., the first author of the research paper.

Participating in the study were 2,000 women, ages 18 to 40, most of whom were Caucasian and lived in Brazil. The team of scientists who conducted the study is based at McGill University in Canada and the Ludwig Institute for Cancer Research in Brazil.

The results suggest that the current method that doctors use for HPV screenings – the Papanicolaou cytology or “pap smear” – should be replaced with a test that detects the presence of a HPV co-infection and identifies each HPV genotype. If an infection is present, the current test cannot determine whether it was triggered by just one genotype or multiple types of HPV.

Because the HPV test used by Franco and his colleagues could detect more than 40 types of the virus and the presence of multiple infections, they could determine the specific genotypes of HPV present in the women’s cervical tissue in single infections as well as co-infections.

The scientists theorized that the multiple viral infections could act synergistically to increase the pre-cancerous mutations or to expedite their progression to cancer. They also suggest that the presence of HPV co-infections may indicate that a woman’s immune system is not particularly effective in clearing viruses.

This new research is the first prospective study using multiple measurements longitudinally to investigate the relationship between multiple HPV types and a woman’s risk for developing pre-cancerous abnormalities in her cervix. During each of the 16,000 patient visits, both the pap smear and HPV tests were administered. The mean follow-up time of the study participants was over three years.

When Franco, Trottier and their colleagues analyzed the data about all patients (women who did not develop pre-cancerous cervical lesions as well as those who did), five HPV types emerged as the most common: 16, 53, 51, 31 and 18. HPV 16’s high prevalence in infections was underscored by the scientists’ analysis of the HPV types that were identified in all of the infections. HPV 16 was found in 9 to 14 percent of single and multiple infections respectively.

Just over 12 percent of the women tested during the first year were infected with multiple HPV types. Over four years, the total increased to more than 22 percent. None of the HPV types were more involved than other types in co-infections. In future studies, the scientists hope to pinpoint the particular combinations of HPV types that characterize the high-risk co-infections.

Editors Note: A PDF of the article is available. Please e-mail communications@aacr.org to request a copy.

# # # #

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 60 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:

Warren Froelich
215-440-9300 ext. 198
froelich@aacr.org

AACR Awards $2.6 Million in Grants for Metastatic Colon Cancer Research

registration@aacr.org () — Fri, 07 Jul 2006 12:00:00 GMT

PHILADELPHIA – The American Association for Cancer Research announces the first 11 recipients of the new Jeannik M. Littlefield-AACR Grants in Metastatic Colon Cancer Research. The awards, ranging to $250,000, were established in February 2006, to support innovative research projects designed to accelerate the discovery and development of new agents to treat metastatic colon cancer. Grant awards were selected through a rigorous and highly competitive process by a committee of accomplished senior scientists. AACR is currently distributing a total of $2,644,977 to the successful investigators.

“Among the 114 applications submitted, these 11 awardees were judged to have the most merit,” said David Irwin, Ph.D., managing director of the Science and Education Division of the AACR. “We offer our sincere congratulations to the investigators, and anticipate they will make substantial contributions to this field of cancer research.”

The Jeannik M. Littlefield-AACR Grants in Metastatic Colon Cancer Research are sponsored by Jacques and Sandy Littlefield of Portolo Valley, California, who donated $3 million to the AACR in late 2005. They are named for Mr. Littlefield’s mother.

Recipients of the 2006 Jeannik M. Littlefield-AACR Grants in Metastatic Colon Cancer Research are:

Peter Carmeliet, M.D., Ph.D., Flanders Interuniversity Institute for Biotechnology, “Preclinical Development of anti-P1GF Antibodies for Metastatic Colon Cancer." In the quest to block angiogenesis, this study will test a homologue of VEGF – P1GF. Antibodies to P1GF will be used in cell lines and xenograft models. The approach has strong potential for clinical application because blocking P1GF should not interfere with normal angiogenesis.

Steven A. Curley, M.D., University of Texas M.D. Anderson Cancer Center, "Carbon Nanotubules and Gold Nanoparticles as Radiofrequency Targets." The goals are to couple antibodies to nanotubules and gold particles to effect specific homing to metastases. Inoperable metastases can then be thermally ablated using microwaves.

Wafik El-Deiry, M.D., Ph.D., University of Pennsylvania, "Novel Therapy for Resistant Metastatic Colon Cancer." The goals are to define the mechanisms in colon cancer that make tumor cells resistant to apoptosis, and develop combination drug therapies that can reverse the apoptotic defect.

Edgar G. Engelman, M.D., Stanford University, "T-Cell Signaling in Metastatic Colon Cancer." This study will examine the failure of the immune system to detect colon cancer cells with the goal of identifying and profiling tumor-associated signaling abnormalities in T-cells. This will affect choice of therapy and will show whether signaling abnormalities can be reversed using immunotherapy.

Douglas V. Faller, M.D., Ph.D., Boston University School of Medicine, "PKC-Delta as a Therapeutic Target in Colon Cancer." The approach is to inhibit PKC-delta which is not critical for normal cellular growth but which, in tumor cells, inhibits Ras-mediated apoptosis. Molecular strategies will identify more active and more specific inducers of the Ras-mediated apoptotic pathway.

Robert D. Ladner, Ph.D., University of Southern California, "Histone Deacetylase Inhibitors for the Treatment of Metastatic Colon Cancer." New approaches will be developed to enhance the effectiveness of 5FU using histone de-acetylase inhibitors.

Eric Lagasse, Ph.D., PharmD, University of Pittsburgh, "Metastatic Colon Cancer, Stem Cells and Bioreactors." Using an artificial bioreactor that models the environment in liver and colon cancer, stem cells will be identified and expanded in vitro. Therapy will then be refined and customized preclinically before being administered to patients.

Nouri Neamati, Ph.D., University of Southern California, "Preclinical Development of SC144 in Metastatic Colon Cancer." A new agent, SC144 has been shown to cause up-regulation of IL24 - a very potent anticancer protein. SC144 will be fully evaluated in mouse models and then, potentially, trials will be extended to humans.

Boris C. Pasche, M.D., Ph.D., Northwestern University, "Targeting the TGFBR1*6A in Metastatic Colon Cancer." This study will use antibodies to TGFB and assess their effects on colon tumor growth in mice. A humanized antibody will be used in a Phase I/II clinical trial.

Gary K. Schwartz, M.D., Memorial Sloan Kettering Cancer Center, "Targeting the Notch Signaling Pathway in Metastatic Colon Cancer." The effectiveness of combining notch and ras inhibitors such as gamma secretase inhibitors will be examined in colon cancer cells as a prerequisite to designing a Phase I clinical trial.

Oliver Stoeltzing, M.D., Universitaet Regensburg, "The Role of Hsp 90 in Hepatic Growth of Colorectal Cancer Metastases." Using colon cell lines and xenografts, this study will examine the role of tissue hypoxia in colorectal hepatic metastases and the suitability of targeting Hsp 90 for molecular targeted therapies.

# # #

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 60 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.

Pomegranate Juice Slows PSA Acceleration Rate After Prostate Cancer Surgery, Radiation

registration@aacr.org () — Sat, 01 Jul 2006 12:00:00 GMT

PHILADELPHIA – Pomegranate juice packs a punch on prostate cancer that prolongs post-surgery PSA doubling time, drives down cancer cell proliferation and causes prostate cancer cells to die, according to a study published in the July 1 issue of Clinical Cancer Research.

Researchers at the Jonsson Cancer Center at UCLA reported that patients with recurrent prostate cancer who drank pomegranate after surgery or radiation treatment saw their PSA blood content levels double after about 54 months. By comparison, PSA levels in the same patients prior to drinking the daily doses of eight-ounce pomegranate juice accelerated more quickly, doubling their PSA levels in only 15 months.

PSA, or prostate specific antigen, is a protein marker for prostate cancer. The faster PSA levels increase in the blood of men after treatment, the greater their potential for dying of prostate cancer.

“The velocity of the increase in PSA is decreased by 35 percent among those who drank the pomegranate juice,” said Allan Pantuck, M.D., associate professor, Department of Urology, David Geffen School of Medicine, UCLA, and lead author of the paper.

“We are hoping that pomegranate juice offers a novel strategy for prolonging the doubling time in men who have been treated for prostate cancer,” Dr. Pantuck added.

According to the study, sera from patients after treatment yielded a net decrease of almost 30 percent in the numbers of prostate cancer cells raised in culture. Similarly, cultured sera from these patients decreased cell proliferation by 12 percent, compared to cells grown with sera from the men taken prior to initiation of the pomegranate treatment program. In addition, treated sera induced 17 percent more programmed cell death, or apoptosis, than sera from the men prior to treatment.

Additional exploratory experiments conducted by Dr. Pantuck and his colleagues examined antioxidant characteristics of the fruit juice.

“Pomegranate is high in antioxidants, and there is good evidence that inflammation plays an important role in prostate cancer,” he said.

Dr. Pantuck and his colleagues detected a 23 percent increase in nitric oxide sera content from patients after they began their daily pomegranate regimen. These studies were conducted in the UCLA laboratory of Louis Ignarro, Ph.D., the Nobel laureate who contributed key scientific findings to define the role of nitric oxide in health and disease.

As with vitamin C and other antioxidants, ellagic acid – a primary antioxidant in pomegranate juice – works to quench molecules that oxidate, or add oxygen, to cellular and circulatory proteins and fats, altering their biological function.

“By quenching oxidative species with antioxidants, you are basically preserving circulating nitric oxide, so it can have a greater biologic effect,” Dr. Pantuck said. “By decreasing the amount of free radicals, you are probably decreasing the circulating factors that are destroying nitric oxide.”

While their findings on nitric oxide, cell proliferation and apoptosis served as exploratory endpoints, Dr. Pantuck stressed that clinical trials with more precise design are necessary to confirm the biological role the fruit plays in prolonging or preventing recurrence of prostate cancer in men.

“We don’t believe we are curing anyone from prostate cancer,” he said. “In our initial trial, although a third of patients experienced a decrease in their PSA during the study, nobody’s PSA went to zero.

“The PSA doubling time, however, was longer. For many men, this may extend the years after surgery or radiation that they remain recurrence free and their life expectancy is extended. They may be able to prevent the need to undergo additional therapies, such as radiation, hormonal or chemotherapies.”

Dr. Pantuck’s colleagues who contributed to this study included Ignarro, John Leppert, Nazy Zomarodian, William Aronson, Jenny Hong, James Bernard, Navindra Seeram, Harley Liker, Hejing Wang, Robert Elashoff, David Heber, and Arie Belldegrun from the departments of Urology, Medicine, Physiologic Science or Biomathematics at the David Geffen School of Medicine, UCLA. Michael Aviram from the Technion Faculty of Medicine, the Rambam Medical Center, Bat – Galim, Haifa, Israel, also contributed to these studies.

Funding to support these studies came from the Lynda and Stewart Resnick Revocable Trust. The Resnicks are the owners of the POM Wonderful Company. Additional NIH funding (P50CA92131 and IR01CA100938) supported portions of the science conducted in the course of these experiments.

Editors Note: A pdf copy of this article is available. Please e-mail communications@aacr.org to request a copy.

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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 60 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 ADVISORY: Cancer Researchers Meet With Congressional Leaders

registration@aacr.org () — Mon, 26 Jun 2006 12:00:00 GMT

CANCER RESEARCHERS MEET WITH CONGRESSIONAL LEADERS TO RAISE AWARENESS ABOUT PROGRESS IN PREVENTION, DETECTION AND TREATMENT

Leading cancer center directors and researchers from around the country will convene in Washington D.C. on Wednesday, June 28 to raise awareness on the latest opportunities and advancements in cancer research.

The event, “Cancer Research: Benefiting All Americans,” will consist of 50 prominent leaders in the cancer community visiting with their Members of Congress to discuss how recent advancements in cancer research are leading to more effective therapies, improved early detection methods, and innovative mechanisms of cancer prevention.

The day is designed to show that federal support for research not only improves overall public health, but also reduces the long-term economic burden of healthcare, helping to maintain the United States as a global leader in scientific advancement.

Co-hosted by the American Association for Cancer Research (AACR), Association of American Cancer Institutes (AACI), and Friends of Cancer Research (FOCR), the day of educational meetings will conclude with an evening reception at the Capitol.

For questions or more information, please contact Jeff Coughlin, Director of Government Affairs at FOCR, at (202) 944-6643 or jcoughlin@focr.org.

Nominations Open for 2007 Landon-AACR Prizes

registration@aacr.org () — Wed, 07 Jun 2006 12:00:00 GMT

PHILADELPHIA – The American Association for Cancer Research is pleased to invite nominations for the sixth annual Landon-AACR Prizes for Basic and Translational Cancer Research. Nominations will be open until August 10, 2006.

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.

The recipient of each prize will receive an unrestricted cash award of $200,000. Both will present lectures during the 98th AACR Annual Meeting, April 14-18, 2007, in Los Angeles, 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 2008. For further information on the nomination process and other details about the prizes, please click here. Inquiries regarding this award should be directed to awards@aacr.org.

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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 60 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. It’s 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.

Media Contact:
Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

Award Information:
Sheri Ozard
215-440-9300, Ext. 114
ozard@aacr.org

Carcinogens from Parents’ Tobacco Smoke Found in Their Babies Urine

registration@aacr.org () — Fri, 12 May 2006 12:00:00 GMT

PHILADELPHIA -- When mom or dad puffs on a cigarette, their infants may inhale the resulting second-hand smoke. Now, scientists have detected cancer-causing chemicals associated with tobacco smoke in the urine of nearly half the babies of smoking parents.

“The take home message is, ‘Don’t smoke around your kids,’” said Stephen S. Hecht, Ph.D., professor and Wallin Chair of Cancer Prevention at The Cancer Center at the University of Minnesota.

According to a study of 144 infants, published in the May issue of Cancer Epidemiology, Biomarkers & Prevention, Hecht and his colleagues found detectable levels of NNAL* in urine from 47 percent of babies exposed to environmental tobacco carcinogens from cigarette smoking family members. NNAL is a cancer-causing chemical produced in the human body as it processes NNK**, a carcinogenic chemical specific to tobacco.

“The level of NNAL detected in the urine of these infants was higher than in most other field studies of environmental tobacco smoke in children and adults,” Hecht said.

“NNAL is an accepted biomarker for uptake of the tobacco-specific carcinogen NNK. You don’t find NNAL in urine except in people who are exposed to tobacco smoke, whether they are adults, children, or infants.”

A previous study by Hecht and his colleagues indicated that the first urine from newborns whose mothers smoked during pregnancy contained as much as one-third more NNAL compared to the babies in the current study. The newborn infants, however, took in the carcinogen directly from their mothers through their placentas rather than by breathing second-hand smoke in the air in their family homes and cars.

In the current study, when babies had detectable levels of NNAL, Hecht said that family members smoked an average of 76 cigarettes per week, in their home or car while the babies were present. In children of smokers whose babies had undetectable levels of NNAL in their urine, the average number of cigarettes smoked by family members was reported at 27 per week.

“With more sensitive analytical equipment, the NNAL from urine of babies in lower frequency cigarette smoking households would most likely be detectable,” Hecht said.

While studies have not determined how the long term risk of exposure to cancer-causing tobacco smoke affects the genetics of babies during their early years when they are growing rapidly, Hecht said that this study demonstrated substantial uptake of NNK and its metabolite NNAL in infants exposed to environmental tobacco smoke.

“These findings support the concept that persistent exposure to environmental tobacco smoke in childhood could be related to cancer later in life,” he said.

Hecht conducted his study in collaboration with Steven G. Carmella, Ky-Ahn Le, Sharon E. Murphy, Angela J. Boettcher, Chap Le, Joseph Koopmeiners, Larry An, and Deborah J. Hennrikus from the Transdisciplinary Tobacco Use Research Center and The Cancer Center, University of Minnesota.

* 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
** 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

Editors Note: Click here to download the PDF of this article.

# # # #

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 60 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:

Russell Vanderboom, Ph.D.
215-440-9300 ext. 120
vanderboom@aacr.org

Candidates Sought for Cancer Prevention Research Award

registration@aacr.org () — Thu, 04 May 2006 12:00:00 GMT

Nominations Open until June 30, 2006

PHILADELPHIA – Nominations are open for the annual American Association for Cancer Research-Cancer Research Prevention Foundation Award for Excellence in Cancer Prevention Research.

In order to qualify, researchers must have made seminal contributions in the conduct of basic, translational, clinical, epidemiological or behavioral research in cancer prevention. The award is intended to recognize not only a major impact on the field, but also the stimulation of a new direction in this important area.

All cancer researchers who are affiliated with any institution involved in cancer research, cancer medicine, or cancer-related biomedical science, anywhere in the world, are eligible. Such institutions include the academic, industrial and government sectors. Candidates also must currently maintain an active research program and have a record of recent publications.

The award will be presented to an individual investigator, who will deliver a lecture at the Fifth Annual AACR International Conference on Frontiers in Cancer Prevention Research, Nov. 12-15, 1006, at the Hynes Convention Center in Boston, Mass.

Information on how to submit a nomination is available on the AACR website at www.aacr.org/page3754.aspx.

The AACR is pleased to co-sponsor this award with the Cancer Research and Prevention Foundation. CRPF is a national, nonprofit health foundation with a single mission: the prevention and early detection of cancer through scientific research and education. Over the years, CRPF has made major contributions to ongoing programs of the AACR and therefore has been named “Champion of the AACR.”

Previous award recipients are: Scott M. Lippman, M.D., The University of Texas M. D. Anderson Cancer Center, Houston, in 2005; David S. Alberts, M.D., University of Arizona Cancer Center, Tucson, in 2004; Waun Ki Hong, M.D., The University of Texas M. D. Anderson Cancer Center, Houston, in 2003; and Michael B. Sporn, M.D., Dartmouth Medical School, Hanover, N.H., in 2002.

# # # #

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 60 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:

Sheri Ozard
215-440-9300 ext. 114
ozard@aacr.org

Inflammation Markers Identify Fatigue in Breast Cancer Survivors

registration@aacr.org () — Mon, 01 May 2006 12:00:00 GMT

PHILADELHPIA -- Researchers at the University of California, Los Angeles have defined conditions associated with disabling fatigue that persists for years in almost a third of breast cancer survivors, according to a study in the May 1 issue of Clinical Cancer Research.

The key to their fatigue stems from responses within their immune systems.

“These studies identify a biological basis for persistent fatigue in cancer survivors that is implemented by inflammation,” said Michael Irwin, M.D., director and senior research scientist, Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, and the UCLA Jonsson Cancer Center.

“We have detected a biological marker that is a composite of two immune response elements,” he added. “This biomarker identifies – and can predict – which women have long term persistent fatigue.

“These findings point the way for development of novel treatment strategies that decrease this inflammatory response and thwart the fatigue that these patients endure.”

One component of the marker, Dr. Irwin explained, is a measure of the amount of interleukin-6 receptor (IL-6R) free-floating in the blood of breast cancer survivors compared to the amount of that receptor remaining on the membranes of specific blood cells – where the receptor normally is found and functions within the immune response.

The IL-6R is usually embedded on the surface membrane of white blood cells, or monocytes. In some survivors, however, many of the IL-6R are shed from the monocytes and are soluble within the blood plasma. Those free-floating receptors can still bind to circulating cytokine IL-6, Dr. Irwin noted, and in that form have the potential to interact with cells that normally don’t respond to cytokine/receptor activation – such as brain cells that may regulate fatigue sensation.

IL6 is a biological chemical that helps drive initial immune responses within people. “IL-6 contributes to an activation of monocytes in the blood, and enables antigen presenting cells to activate T cells as part of the cellular immune response,” Dr. Irwin said.

The second component of the marker is an index measured by the level of T cells that are characterized by CD69, a cell membrane protein that indicates early activation of those T cells. Patients with a decreased number of CD69+ T cells along with the high ratio of serum IL-6R/monocyte-bound IL-6R were likely to experience persistent fatigue.

Battling breast cancer is a daunting challenge to women diagnosed with the disease, but with advanced screening and treatment strategies, patients with early stage breast cancer are surviving longer. Breast cancer survivors are the largest group of patients to overcome any type of cancer in the United States. While patients surviving other types of cancer also can experience the long-lasting fatigue syndrome, a greater proportion of breast cancer survivors endure the condition.

Cancer researchers had explored various possible reasons for the persistent fatigue in breast cancer survivors, Dr. Irwin said, such as different kinds of treatment, or biological events including anemia. Dr. Irwin and his colleagues’ research is the first to document an association between biological mechanisms involved with the immune response and persistent fatigue.

“It is such an important quality of life issue. Many patients are surviving from their cancer treatments, but they are surviving with substantial impairments in their ability to carry on their lives,” Dr. Irwin said. “We’ve addressed the cancer in these survivors, and now we can also address the functional declines in the quality of life of these patients.”

Dr. Irwin defined the fatigue biomarker in collaboration with Alicia Collado-Hidalgo, Julienne E. Bower, Patricia A. Ganz, and Steve W. Cole, with the David E. Geffen School of Medicine at UCLA.

# # # #

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 60 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:

Russell Vanderboom, Ph.D.
215-440-9300 ext. 120
vanderboom@aacr.org

Cancerous vs. Healthy Cells: Researchers Identify the Road to Success

registration@aacr.org () — Wed, 05 Apr 2006 12:00:00 GMT

Studies Determine Best Route for Targeted Therapies

WASHINGTON, D.C. − Conventional cancer treatments are generally effective in wiping out tumor cells, but in the process they also may kill healthy cells. Researchers are focusing their efforts now on treatments that can target just the cancerous cells, without harming healthy tissue in their midst. These new types of drugs are known as targeted therapies, and physicians are studying their effectiveness and possible side effects in a variety of different types of cancer. Several targeted therapies are being studied alone and in combination to treat a variety of cancer types. In particular, cancerous brain tumors can be more difficult to treat than other cancers, and oncologists are developing therapies that target these cells to improve patients' survival. Researchers also are gaining a better understanding of the molecular differences between cancerous and healthy cells, improving current treatment and survival rates, according to studies presented today at the 97th Annual Meeting of the American Association for Cancer Research.

NF-kappa B as a Therapeutic Target in Malignant Gliomas: Abstract No. 1506

Researchers from the National Cancer Institute in Bethesda, Md., have found they may be able to successfully treat brain tumor cells with a new targeted therapy that inhibits the activity of a cell protein called nuclear factor-Kappa B (NF-kappa B). The drug, called bortezomib or (Velcade®) – when used alone or in combination with other cancer treatments – represents a potential new way to treat malignant glioma, a particularly stubborn and aggressive brain tumor.

“Targeting the NF-kappa B pathway either alone or in combination with other chemotherapy agents, is an effective anti-glioma treatment,” said Ai-Min Hui, M.D., Ph.D., research fellow at the NCI and the lead investigator of the study.

In their study, the NCI researchers set out to determine the role of NF-kappa B in reversing the apoptotic (or programmed cell death) effect of selective estrogen receptor modulators (SERMs) in brain cancer, as well as potential therapies that can be used either alone or in combination to block the protein. High levels of NF-kappa B are activated and present in transplanted glioma cells and glioma tumor samples, but not in normal brain tissue cells.

SERMs have shown some value in inducing cell death in brain cancers by a previously unknown method. They are designed to deliver the benefits of estrogen without its negative side effects, although gliomas do not generally express the estrogen receptor. However, previous studies have shown that NF-?B protects glioma cells from breaking down, therefore reversing the effect of SERM therapies.

Researchers looked at 203 glioma samples and determined that NF-kappa B was activated. They also noticed that the level of activation was related to the grade of the tumor, suggesting that NF-kappa B is related to tumor progression. Treatment with bortezomib suppressed both unregulated and signal-oriented activation in NF-kappa B by inhibiting the breakdown of IkB-alpha. IkB-alpha is one of a series of inhibitory proteins that controls the activation of NF-kappa B, preventing it from binding to DNA in the nucleus. Bortezomib not only stops the degradation of IkB-alpha, it also suppresses the activation of NF-kappa B, thus stopping cell growth.

“By interfering with the function of I kappa B-alpha proteins, bortezomib was shown to induce glioma cell degradation and enhance anti-cancer effects of SERMs,” said Ai-Min Hui, M.D., Ph.D., research fellow at the National Cancer Institute and lead investigator on this trial.

“New studies looking at the combined use of bortezomib and high-dose tamoxifen may provide a viable treatment option for patients with recurrent, high grade malignant gliomas,” he said.

Malignant gliomas are one of the most common brain tumors, accounting for more than half of the 18,000 primary cancerous brain tumors diagnosed annually in the United States, and are the fourth most common cause of cancer death in patients aged 15 to 44.

Standard treatment for patients diagnosed with brain cancer is surgery followed by radiation, sometimes with added chemotherapy. However, current therapies are considered inadequate to fight this deadly disease and researchers have been trying to identify new targets and develop new agents with different mechanisms of action to help increase patients’ survival.

PTEN-Loss Mediated Herceptin (trastuzumab) Resistance and Targeting the PI3K Pathway as a Counteracting Strategy: Abstract No. IS-445

Researchers from The University of Texas M. D. Anderson Cancer Center, Houston, have identified why some women with Her-2 positive breast cancer, an aggressive form of the disease, do not respond to the drug trastuzumab (Herceptin®) or may actually develop a resistance to the treatment. The investigators discovered that a combination of trastuzumab and a new kinase inhibitor, PI3K, may work together to increase these patients’ chances of survival.

Trastuzumab treats women with metastatic breast cancer whose tumors overproduce the ErbB2 gene. The overproduction of the ErbB2 gene, also called Her-2/neu, leads to aggressive breast cancer and poorer patient survival. ErbB2 is part of a family of genes called epidermal growth factor receptors (EGFR) that stimulate cell growth and division. Trastuzumab has shown outstanding efficacy for patients with high levels of the ErbB2 gene.

Approximately one-third of patients who possess the ErbB2 gene will respond to trastuzumab therapy, but the treatment is sometimes combined with other chemotherapy agents to make it more effective. Still other patients develop resistance to the therapy over time.

In this study, researchers found that loss of PTEN can lead to resistance of trastuzumab. The PTEN gene (phosphatase and tensin homolog deleted on chromosome ten) acts as a tumor suppressor gene, helping to regulate the cycle of cell division by keeping cells from growing and dividing uncontrollably or too rapidly, and ultimately forming tumors. Normally, the PTEN enzyme acts as part of a chemical pathway that signals cells to stop dividing and causes cells to undergo apoptosis. However, reduced levels of PTEN contribute to trastuzumab resistance, both in vivo (humans and mice) and in vitro (culture). Patients with PTEN-deficient breast cancer have poorer outcomes and response to trastuzumab therapy when compared to those with normal PTEN levels.

The researchers then examined the role played by phosphoinositide 3-kinase (PI3K) pathway inhibitors to reverse PTEN-reduction-mediated trastuzumab resistance. PI3K regulates several key signals that initiate cell processes frequently disrupted by carcinogenesis, a process by which normal cells are transformed into cancer cells. Seven PI3K pathway inhibitors, either currently in use or under development in clinical trials, were examined. One inhibitor used in combination with trastuzumab successfully inhibited cell growth, and a second, when used with trastuzumab, sensitized the therapeutic effects of the drug. Researchers said the next step is to conduct a phase I/II study looking at these combinations in patients who did not respond to traztuzumab as a first-line therapy.

“PTEN seems to be a very sensitive and specific predictor to trastuzumab-based therapy and data suggest that activation of PTEN is a novel mechanism underlying the anti-tumor activity of trastuzumab. Combination therapy may provide more effective therapeutic regimens, allowing more patients to benefit from trastuzumab,” said Dihua Yu, M.D., Ph.D., professor in the department of surgical oncology and director of research in the Surgery Division, The University of Texas M. D. Anderson Cancer Center.

A Novel, Potent and Selective IGF-1R Small Molecule Inhibitor Blocks Activation of IGF-1R Signaling in Vitro and Inhibits IGF-1R Dependent Tumor Growth in Vivo: Abstract No. LB-281

Researchers from OSI Pharmaceuticals have identified a new small molecule inhibitor that may stop the growth of colon cancer. In this study, investigators discovered and tested an IGF-1R inhibitor, referred to as Compound 1.*

Compound 1 was shown to hinder the signaling response of IGF-1R -- specifically blocking the activation of two downstream pathways, stopping tumor cell growth and survival. The study also showed that the colon cancer tumors respond to the drug because they produce and are dependent on the growth-promoting effects of IGF-II.

"We are very encouraged by the results seen in our pre-clinical IGF-1R inhibitor program. The most important finding of our study was that, when administered orally, our IGF-1R inhibitor prevented the growth of human colon cancer tumors in mice,” said Jonathan A. Pachter, Ph.D., senior director of cancer biology, OSI Pharmaceuticals, Long Island, N.Y.

Insulin-like growth factor 1 receptor (IGF-1R) is a cellular protein with a molecular structure similar to that of the receptor for insulin, a hormone that regulates the amount of glucose sugar in the blood. The IGF-1R has been shown to play roles in tumor cell growth and the inhibition of cell death. There are two circulating proteins (or ligands) that activate the IGF-1R (IGF-I and IGF-II). The excess production of IGF-II is thought to encourage tumor growth.

Certain tumors, including colorectal, non-small cell lung, ovarian and some cancers in children, drive their own growth and survival through the overproduction of IGF-II. This IGF-II activates the IGF-1R on the surface of cancer cells to stimulate tumor growth, making IGF-1R an important treatment target for many human cancers.

“This small molecule represents a potent and selective IGF-1R kinase inhibitor that could be effective in the treatment of IGF-II driven human cancers," said Dr. Pachter.

A variety of approaches to block IGF-1R signaling have been used to cause cell death in a broad range of cancers, both in cell cultures and live models. Through the use of structure-based design, OSI Pharmaceuticals has been able to identify small molecules that selectively block the ability of IGF-1R to increase cell growth.

Another major challenge in the development of IGF-1R inhibitors is to avoid blocking the closely related insulin receptor that regulates glucose levels in the blood. Results from the study showed that in addition to diminishing or halting tumor growth in human cancer cells transferred to live test animals, OSI's IGF-1R inhibitor showed no substantial rise in blood sugar.

* Compound 1’s formal name is: cis-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-1-(2-phenyl-quinolin-7-yl)- imidazo[1,5-a]pyrazin-8-ylamine.

# # #

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 60 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.

Contact:

Warren Froelich
215-440-9300 ext. 198
froelich@aacr.org

Markers of Gene, Protein, or Micro-RNA Activity Predict Outcome in Prostate and Colorectal Cancers

registration@aacr.org () — Wed, 05 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. -- Cancer researchers are working toward a future in which each patient's tumor will act like a crystal ball, revealing how
oncologists should treat the cancer to obtain the best outcome. Currently, physicians cannot predict which patients with prostate cancer should
receive extra therapy after surgery; or whether some of these patients have an indolent disease that does not even require surgery. Most patients with
colorectal cancer have surgery, but some, even at the earliest stages, could benefit from additional treatment, if physicians only knew who. Some of the
genes and proteins specific to cancer cells can be used for prognostic purposes, as can the newest type of biomarker, mcro-RNAs, according to
studies presented today at the 97th Annual Meeting of the American Association for Cancer Research.

The Serological Markers TIMP-1, PAI-1, MASP-2 and CRP are Independent Predictors of Colorectal Cancer-Specific Death: Abstract No. 5723

Oncologists say it is very difficult to predict which patients with colorectal cancer will be cured by surgery alone − the single treatment most patients
receive − and who might benefit from the addition of chemotherapy. Now, however, a Danish research team has found that just four protein biomarkers
can predict death from colorectal cancer, independent of the stage or location of the cancer, or the age or gender of the patient.

In this study, blood taken from 654 colorectal cancer patients just before they had surgery was retrospectively analyzed for expression of the proteins.
The test was not perfect, but it significantly identified the 308 patients who later died of the disease, some up to nine years later.

"The results show that the outcome of a significant number of patients was correctly identified, independent of stage and location," said the lead author,
Hans J. Nielsen, M.D, DMSc., Professor of Surgical Oncology, at Hvidovre University Hospital.

When tumor stage and location were factored into the test, the concordance between predicted survival and actual survival was 79 percent, Nielsen said.
Latest in Prognosis Presented at AACR Annual Meeting. Such a test could offer prognostic value to clinicians who are unsure whether to treat their newly
diagnosed patients with surgery alone, he said.

"This protein profile might be used to identify groups of patients who, independent of stage, should be offered adjuvant chemotherapy, and groups of patients who should not be offered chemotherapy," Nielsen said. "Such possible patient differentiation should, of course, be confirmed in prospective
studies."

Such a study is currently underway in Denmark and other Scandinavian countries, he said. Up to 1,500 patients will be enrolled and blood samples will
be collected periodically, such as before and after every treatment. The four protein markers will then be validated for disease stage, primary and
secondary treatment, recurrence, and survival, and may prove to be predictive of response to individual therapies, as well as survival, Nielsen said.
The protein markers included in the test − TIMP-1, PAI-1, MASP-2, and CRP −are related to tissue remodeling, angiogenesis, and inflammation. The test
uses antibodies that specifically bind to the proteins, and can analyze the actual concentration of these proteins.

MicroRNA Signature for the Human Colonic Crypt Base Region is Predictive of Colon Cancer: Abstract No. LB-6

Most researchers use gene or protein "chips" to define cancer processes, but researchers at Thomas Jefferson University in Philadelphia took a novel
approach using a micro-RNA (miRNA) chip to help them understand how colon cancer develops. They found a distinct "signature" in the expression of
miRNAs that predicts colon cancer.

Scientists have only recently discovered that miRNAs, which are tiny snippets of single-stranded RNA, can regulate the expression of genes, and thus
regulate protein synthesis that affects cellular pathways. Because of this ability to regulate gene expression, miRNAs are believed to play an important
role in cancer development, and could serve as targets for novel anti-cancer drugs.

To discover which miRNAs are expressed in colon cancer, compared to normal colon tissue, researchers at Thomas Jefferson University used a microarray chip containing probes for most of the known miRNAs in human and mouse. The investigative team, led by Bruce Boman, M.D., Ph.D., director of Genetic and Preventive Medicine at Jefferson, used the array to first characterize the miRNA expression pattern in intestinal epithelium purified from normal colon tissue.

This epithelial inner lining of the colon contains about 50 million test-tube shaped crypts that line the colon. Colon cancer arises in these crypts, and
researchers believe that the cells of origin are the 10-20 immortal stem cells that reside at the bottom of each crypt. The job of these stem cells is to
replenish the entire lining of the colon that turns over every five days.

However, a mutation in these stem cells produces mutant daughter cells, disorganized tissue architecture, and increased proliferation of crypt cells,
which leads to development of colon tumors, Boman said.

Hence, they then analyzed malignant colon tissues and found that there are a number of miRNAs that were changed in expression in colon cancer.
Boman, who also directs the G.I. Cancer Program at Jefferson's Kimmel Cancer Center, next purified and microdissected colonic crypts, and compared miRNA expression between the bottom tenth of the crypt, where the stem cells reside, and the upper 9/10s of the crypt.

The difference in miRNA signatures between these two crypt regions, they reasoned, would distinguish stem cell from non-stem cell activity. They found
a distinct signature of 16 miRNAs that characterizes the crypt bottom. Further analysis revealed that the expression pattern of these 16 miRNAs
accurately predicted which colon tissues were normal and which cancerous.

"Because this subset of miRNAs is differentially expressed at the crypt bottom, these miRNAs may be involved in regulating crypt stem cell
population dynamics and contribute to the stem cell origin of colon cancer," Boman said.

"Our finding of a difference between miRNA expression in normal versus cancerous colon tissues should provide insight into mechanisms of colon cancer development and identify novel drugs to treat the disease" he said.

Expression Profiles of 16 Genes Predict Prostate Carcinoma Relapse and Disease Free Survival in Formalin-Fixed, Paraffin-Embedded (FFPE) Benign and Prostate Carcinoma Tissues Using Universal Bead Arrays: Abstract No. 1203

Researchers say that a chip that measures expression of 16 genes provides much needed prognostic information for prostate cancer patients who fall in
the "gray zone" of traditional tests.

This experimental "universal bead array" test, which is designed to be low cost and easy to administer, appears to be a better predictor of relapse and
disease-free survival than the Gleason Score, according to lead author Jessica Wang-Rodriguez, M.D., associate clinical professor of Pathology at
the University of California, San Diego.

The 50 year-old Gleason Score, which assigns a progressive score of 1-10, based on how differentiated the cells look in a prostate cancer sample, works
fairly well when the score is either very low or very high, but the prognosis for men who have scores in the mid-range is difficult to predict, Wang-
Rodriguez said.

"It is very difficult to predict relapse and cancer recurrence in men who have a score of 6 or 7," she said. "Half of patients with these scores do well, and
the other half don't, but we cannot now predict who will fall into those groups."

Believing that a gene microarray test might provide additional information, a team of researchers led by Wang-Rodriguez picked 512 genes from the
scientific literature that seemed to play a role in prostate cancer. They tested their expression on paraffin-embedded tumor samples taken from
71 patients, as well as on 41 control samples (non-cancerous prostate tissue taken from the same group of patients).

From this, they identified 16 candidate genes to further analyze. Ten of the genes were positively correlated to cancer progression, and six were
negatively correlated, she said, and when tested, the combination generated a gene expression score that provided a better predictor of relapse
than the Gleason score. "This gene expression score appears to give us additional prognostic information that current technology cannot provide, and
that will help us treat patients accordingly," she said.

The assay they used was developed by Illumina Inc., of San Diego, which also funded this study. It uses fine optic beads and needs only tiny amount of DNA and RNA, Wang-Rodriguez said, and up to 96 different tests can be put on a single tray. "Having batches of samples together in a single assay
that can then be read automatically makes it easy for routine clinical use," she said.

"The test has a lot of potential, but needs to be further studied and validated."

Methylation Markers Are an Independent Predictor of Prostate Cancer Prognosis in a Cohort of 605 Radical Prostatectomy Patients: Abstract No. LB-226

Researchers have found that a test checking the methylation of a single gene can predict recurrence of prostate cancer in patients who have had their
glands surgically removed.

In a clinical study of tumor tissue taken from 605 prostate cancer patients, those who had a positive PITX2 methylation test were three times more likely
to experience cancer recurrence than those who tested negative, according to the study's lead author, Susan Cottrell, Ph.D., senior scientist at
Epigenomics, Inc., in Seattle. Furthermore, the test predicted recurrence in all patient subgroups, including patients with organ-confined and non-organ-
confined disease.

Cancer recurrence was defined in this study as a rise in prostate specific antigen (PSA) levels after surgery, she said. Rising PSA after removal of the
prostate indicates that the cancer is in the process of recurring.

"A methylation test like this could potentially help doctors decide which patients need additional treatment after surgery, and which probably don't,"
said Cottrell. "The test is based on underlying molecular changes involved in cancer development, and this molecular information is complementary to the
clinical and anatomical information currently used to predict recurrence, such as tumor stage and Gleason score."

According to Cottrell, the test will soon be validated in a multi-center trial for submission to the FDA. She also added that while this study analyzed
prostatectomy samples, Epigenomics is expanding its research to see if the same results can be obtained from prostate biopsies. "If the test is a strong enough predictor of a good prognosis at the stage of biopsy, men with indolent cancer may not need surgery or radiation at all," she said.

"We know many men have a non-aggressive form of prostate cancer, but because we currently have no way to those patients, only very few are
treated with a 'watchful waiting' approach instead of surgery or radiation," she said.

The PITX2 gene is believed to play a role in regulation of hormones, and Epigenomics earlier found that it could also help predict recurrence in breast
cancer patients.

In this study, the researchers tested a total of six genetic markers − PITX2 plus five other methylated genes that were identified in tumor tissue taken
from patients who recurred shortly after surgery. Hypermethylation of all six markers correlated with poor survival, but using PITX2 alone, the researchers found they could develop a methylation score that defined a good prognosis (with 94 percent PSA-free survival 10 years after surgery) and a
poor prognosis group (with 70 percent survival).

# # # #

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 60 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.

CONTACT:
Warren Froelich
215-440-9300 ext. 198
froelich@aacr.org
In Washington 4/1-4/5
202-249-4004

Inflammation and Drugs to Control this Activity Studied in a Variety of Tumors Sites

registration@aacr.org () — Tue, 04 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. - Inflammation cuts both ways. When invaded by an infectious agent, for example, the body calls on the forces of inflammation to fight and defeat the intruder. But when the biochemical processes of the immune system are either misdirected or chronically turned on, inflammation can lead to adversity, including some forms of cancer. For this reason, scientists are closely studying the link between inflammatory processes and tumor formation, while others are investigating anti-inflammatory drugs as a means to prevent and treat cancer, as seen by studies presented today at the 97th Annual Meeting of the American Association for Cancer Research.

Antihistamine and Anti-inflammatory Drug Use Associated Differently for High-Grade Versus Low-Grade Gliomas: Abstract No. 486

Individuals who used antihistamines regularly for a six-month period or longer have nearly a three-fold greater risk of developing mid-grade brain tumors, and a two-fold risk of having low-grade tumors. Using anti-inflammatory medications helped protect against developing a deadly brain tumor called glioblastoma.

The researchers, led by Michael Scheurer, Ph.D., postdoctoral fellow in Cancer Prevention and Melissa Bondy, Ph.D., professor of Epidemiology, both at The University of Texas M. D. Anderson Cancer Center in Houston, cautioned that they are not implying that use of antihistamines causes brain tumors, but rather that these medications may be part of a complex milieu of factors that contribute to their development.

Scheurer and Bondy used combined data from two studies: the Harris County Adult Glioma Study and the Bay Area Adult Glioma Study, led by Margaret Wrensch, Ph.D. at the University of California, San Francisco. As part of the studies, participants were asked about their use of antihistamines and anti-inflammatory drugs.

They compared antihistamine and anti-inflammatory drug use in 830 brain tumor cases and 831 controls matched for age, gender and race. The tumors were analyzed by histologic type. The majority – 339 – were high-grade glioblastomas; 117 were mid-grade, or anaplastic astrocytoma; and 154 cases were low-grade.

The scientists found that regular, long-term antihistamine use was associated with an increased risk for developing anaplastic astrocytomas and low-grade brain tumors.

“To our knowledge, this report is the first time that anyone has looked at this particular relationship – the potential effects of antihistamines on the development of brain tumors in adults,” said Scheurer. “It’s apparent that some type of inflammatory response is playing some role in the development of brain tumors. We don’t know exactly what that role is or the specific mechanisms, but we’re on the road to finding out.

“This again points to the fact that brain tumors are caused by a combination of several environmental, endogenous and genetic factors,” he said. “They are not related to one specific cause, but rather, to several that are interplaying with one another to create tumors. We’re trying to figure out what those key factors and genes are and how they interact with one another.”

Scheurer said several studies have reported that people with allergies or asthma have a lower risk of developing glioblastomas. One report showed that those who take non-steroidal anti-inflammatory drugs, or NSAIDs, also have a reduced risk for developing such high-grade tumors. He and Bondy focused on antihistamines because people who have allergies typically take antihistamines.

“We knew that the different types of tumors have different etiologies and different genetic characteristics and we wanted to see if there were differences in risk,” Bondy said.

Scheurer and Bondy are also looking at certain different variations of genes in individuals and how they respond to inflammatory processes in the brain. “We’re hopefully looking at some genes related to inflammatory cytokines and we’ll see how individual response to inflammatory stimuli may increase or decrease a person’s risk of developing a brain tumor,” Scheurer said.

Influence of Chronic Inflammation on Prostate Carcinogenesis: A Five-Year Follow-up Study: Abstract No. 1474

Researchers at Case Western Reserve University in Cleveland have evidence linking chronic inflammation in the prostate to a greater risk of developing prostate cancer. Results of repeat biopsies of prostate tissue over a five-year period from men who had abnormal serum prostate specific antigen (PSA) levels and/or digital rectal examinations (DRE) suggest that chronic inflammation may be a significant risk factor in the development of prostate cancer.

While connections between inflammation and cancer have been shown for some cancers, no one had shown a relation between chronic prostate inflammation and the development of prostate cancer, said Sanjay Gupta, Ph.D., assistant professor of urology at Case Western Reserve University in Cleveland, who led the work along with Greg MacLennan, M.D., associate professor of pathology.

Gupta and his co-workers examined the results of prostate needle biopsies from 177 men between ages 47 and 83 years who were at high risk for developing cancer based on either high PSA scores or abnormal DREs. Of the 177 men, 144 or 81 percent were found to have chronic prostate tissue inflammation.

The scientists categorized the biopsies based on pathology. They found that of the 144 cases, 15 percent (22/144) had only inflammation, 15 percent (22/144) had simple atrophy, 39 percent (54/144) showed PAH/PIA (post-atrophic hyperplasia and/or proliferative inflammatory atrophy, which indicate evidence of chronic inflammation) lesions, and eight percent, or 12/144, showed HGPIN – high-grade prostate intraepithelial neoplasia, which is a precursor to prostate cancer. About 20 percent, or 29/144, had cancer (adenocarcinoma) in the initial biopsies.

The researchers analyzed 84 subsequent biopsies performed within five years in patients who had initially shown chronic prostate inflammation. In the follow up, 29 new cancer cases were diagnosed: six occurred in patients in whom initial biopsies showed only chronic inflammation, 15 in patients with initial PAH/PIA lesions, along with eight in patients with chronic inflammation and other risk factors for cancer (high-grade prostate intraepithelial neoplasia and atypical small acinar proliferation that may have been cancerous).

In contrast, the researchers found only two cases – six percent – in the 33 patients without inflammation who went on to develop cancer, both of whom had other risk factors for cancer.

“We observed a significant association between serum PSA and the degree of chronic inflammation,” said Gupta, which was expected based on previous findings.

“The first concern is, should patients with initial biopsies showing no malignancy but showing chronic inflammation be followed more closely and perhaps re-biopsied more frequently?” Gupta said.

Gupta’s group plans future studies that will be similar in design, but have a larger number of subjects.

COX-2 Expression in Atypia: Correlation with Breast Cancer Risk: Abstract No. 2353

Women with atypical hyperplasia who also have high levels of the enzyme COX-2 in their breast tissue were more likely to develop breast cancer than women with lower levels of the enzyme.

According to Lynn Hartmann, M.D., professor of oncology at the Mayo Clinic College of Medicine in Rochester, Minn., about one million women a year have a breast biopsy with benign findings (sometimes called benign breast disease). One form of benign breast disease, atypical hyperplasia, or atypia, is characterized by abnormal cell growth and can be precancerous. Women with this condition have a four times greater risk of developing breast cancer.

Hartmann and her co-workers wanted to find out whether or not they could use molecular tools, such as COX-2 levels, to predict who among the group of women with atypia would develop breast cancer and develop ways to separate groups of women into high risk and normal risk. The COX-2, or cyclooxygenase-2, enzyme is produced by the body when there is inflammation and is also produced by precancerous tissues.

They took advantage of a tissue bank from the Mayo Clinic Benign Breast Disease Cohort, which includes several thousand women who, between 1967 and 1991, had a benign breast biopsy. Of this group, 235 women had atypical hyperplasia and tissue available for the study. Cancer follow-up information was available for all of these women. Hartmann and her co-workers determined the amount of COX-2 in these samples by staining immunohistochemistry methods. Forty-one of the 235 women with atypia developed breast cancer over roughly a 15- to 20-year period.

The research team found a significantly higher level of COX-2 in atypias of those women who went on to develop breast cancer than they did in control subjects. “Intense COX-2 expression,” Hartmann said, “is associated with a significantly greater likelihood of a subsequent breast cancer in women with atypia. Specifically, for women with strong staining, their risk of breast cancer at 20 years was 31 percent, versus 14 percent for those with negative or weak staining.”

She noted that increased COX-2 expression has also been seen in an early form of breast cancer called ductal carcinoma in situ, or DCIS.

Hartmann said that COX-2 represents a potential target for chemoprevention. Her team plans to expand the test group and will continue to profile women with atypia who did and who did not develop breast cancer in an attempt to identify early predictors of risk.

Reduction in the Risk of Human Breast Cancer by COX-2 Inhibitors: Abstract No. 2352

Results of a five-year study have shown for the first time a significant reduction in risk associated with selective COX-2 inhibitors in human breast cancer.

Randall Harris, M.D., Ph.D., professor and director of the Center of Molecular Epidemiology in the College of Medicine and School of Public Health at The Ohio State University Medical Center in Columbus and his co-workers looked at the use of selective COX-2 inhibitors such as Vioxx and Celebrex between 1999 and 2004 and the incidence of breast cancer.

They compared 323 breast cancer cases to 649 healthy controls and found a risk reduction of about 71 percent with the use of selective COX-2 blockers.

Harris was not surprised. “This was not a surprising result showing selective COX-2 inhibitors would have a significant effect in reducing the incidence of breast cancer,” he said.

A number of studies have shown that people who regularly take non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen to treat conditions like arthritis, have lower rates of colorectal polyps, colorectal cancer, breast cancer and many other cancers. NSAIDs exert anti-inflammatory effects by blocking COX, or cyclooxygenase enzymes, which are produced by the body when there is inflammation and are also produced by precancerous tissues.

“The combined results of 20 human studies of aspirin and ibuprofen reflect an approximate 30 percent reduction in the risk for breast cancer, and animal studies have shown a profound effect by COX-2 blockers against a variety of cancers,” he said.

Harris said that these results have implications for chemoprevention of breast cancer and other cancers. This particular study is a sub-study of four types of cancer, including prostate, lung and colon cancer. The researchers will release data at the meeting showing results consistent with the breast cancer findings.

“There’s a lot of interest in the use of these compounds in therapy and prevention,” Harris noted. “It will be important for investigators to look at these compounds in prospective and retrospective studies to see if these results are consistent.”

“We’re concerned about potential side effects of these agents, and before making specific recommendations for their use, further studies are needed to determine if low dosages that cause no harm have consistent preventive effects against cancer,” Harris said.

COX-2 inhibitors may also have effects in preventing other diseases, and his laboratory would like to explore their effects against cardiovascular and neurodegenerative diseases such as Alzheimer’s disease. He hopes to continue to look at COX-2 blockers at sub-therapeutic doses in chemoprevention.

“We need to look at a broader spectrum of conditions related to the inflammatory cascade and modulating the cascade with these and other compounds.”

Variants in the alpha-Methylacyl-CoA Racemase Gene and the Association with Advanced Distal Colorectal Adenomas in the Prostate, Lung, Colorectal and Ovarian Screening Trial:
Abstract No. LB-344

Researchers have shown that a particular version of a gene that enhances ibuprofen’s anti-inflammatory effects also makes it more effective in preventing the development of potentially precancerous polyps in the colon.

Sarah Daugherty, research fellow at the National Cancer Institute and doctoral candidate at Johns Hopkins Bloomberg School of Public Health and her colleagues looked at seven variants of the gene for alpha-methylacyl-CoA racemase, or AMACR. This protein metabolizes branched chain fatty acids, cholesterol metabolites and enhances the activity of ibuprofen.

The AMACR protein is overexpressed in some cancers such as prostate, colon and precancerous colorectal adenomas, or polyps, though it is expressed very little in normal tissues. According to Daugherty, no one had examined the association between AMACR variants and colorectal adenomas or cancer.

The research team identified 725 white men and women between ages 55 and 74 who had participated in the multicenter, National Cancer Institute-supported Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and who had a sigmoidoscopy that showed a suspicious polyp in the distal colon that was confirmed by a follow-up exam. These participants were compared to 729 control subjects who had a sigmoidoscopy showing no polyps. All subjects completed questionnaires that asked about ibuprofen use and each provided a blood sample.

The scientists looked at the seven gene variants among the two groups. They found that four of seven variants were associated with an increased risk for advanced distal colorectal adenomas. The frequency of these variants was higher among those with polyps than among controls.

The researchers also compared ibuprofen use among the two groups. Studies have shown that non-steroidal anti-inflammatory drugs such as ibuprofen can reduce the risk of adenomas and colorectal cancer.

“We found that regular use of ibuprofen had a slight protective effect in the development of advanced distal colorectal adenomas – a 20 percent reduction in risk, which was not statistically significant,” Daugherty said.

When they looked further at the association between ibuprofen use and colorectal adenomas, they found that a subgroup of individuals who had two copies of one variant showed a statistically significant reduction of nearly 70 percent in the risk for developing adenomas. Among the other individuals who did not have this genotype, regular use of ibuprofen had little effect on risk of colorectal adenomas.

“Our data are the first to show a link between these genotypes and effectiveness of ibuprofen in protecting against adenomas,” Daugherty said. She noted that previous research in animals has shown that AMACR modifies a component of ibuprofen that enhances its chemopreventive effects.

“This is the first study to corroborate the biological data at a statistical level in humans,” she said.

Her team’s results need to be verified in other populations, she said. “While our results are statistically suggestive that there is an association between these variations in the gene and colorectal adenomas, there needs to be biological follow-up so we know the functional relevance of these markers.”

Daugherty said that before AMACR can be used for any potential clinical application, more study is needed to verify the findings and determine relationships to ibuprofen dose, duration and timing.

# # # #

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 60 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.

Contact:

Warren Froelich
215/440-9300, Ext. 198
froelich@aacr.org
In Washington, DC (4/1-4/5)
202/249-4004
202/249-4005 fax

Studies Explore the Many Complex Linkages Between Smoking and Cancer

registration@aacr.org () — Tue, 04 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. - Researchers are delving deeper into the links between smoking and cancer, teasing out the genes and molecules involved as well as other factors that affect cancer risk. They have found, for example, a specific protein that decreases with smoking cessation. Genetic factors are also being implicated in the lung cancers of people who have never smoked. New studies are revealing an association between smoking and ovarian cancer, as well as between second-hand smoke exposure and lung cancer survival. Understanding these diverse connections and how they work -- whether on the molecular, familial, or population level -- helps in understanding cancer risk and outcomes and in crafting programs to help people avoid or quit smoking, according to studies presented today at the 97th Annual Meeting of the American Association of Cancer Research.

The Association Between the Anti-Inflammatory Protein CC10 and Smoking Status Among Participants in a Chemoprevention Trial: Abstract No. 5738

People who have stopped smoking have higher blood levels of a protein called CC10 than those who are still smoking, a finding that may help to explain why former smokers have a lower risk of lung cancer than current smokers.

“We know that smoking cessation is good, that it reduces the risk of lung cancer compared to continuation of smoking, but we don’t know the molecular basis for the lower risk,” said Jiping Chen, M.D., Ph.D., a Cancer Prevention Fellow at the National Cancer Institute, Bethesda, Md. Chen is the lead author of the study, which was the first to demonstrate that CC10 levels, normally high in non-smokers and low in smokers, could be restored after long-term smoking cessation.

CC10 is a protein that is expressed in the lining of the bronchial system. Its biology is not completely understood but it is known to play a role in protecting the lining of the respiratory tract from oxidative damage and inflammation.

To determine whether smoking cessation affects CC10 levels, the researchers measured levels of the protein in 81 current and 23 former smokers. The former smokers had not smoked for about seven years on average. All of the participants had bronchial dysplasia, a precancerous lesion putting them at high risk for lung cancer. CC10 levels were measured in blood samples as well as samples from bronchoalveolar lavage–a procedure that uses a fiberoptic scope to inject sterile saline into the lung and remove the fluid.

After adjusting for age, CC10 levels in the blood of former smokers were 1.7 times higher than those of current smokers, a statistically significant difference. Protein levels in the bronchoalveolar lavage fluid levels were also higher in former smokers, although the difference was not statistically significant. The results were substantially the same after adjusting for sex and pack-years of smoking.

The researchers concluded that sustained smoking cessation is associated with increased blood levels of CC10. “This is good news for former smokers,” said Chen. “It provides more evidence that quitting smoking can undo some of the damage to the lung resulting from tobacco exposure.”

The researchers’ next step may be to look at CC10 levels in a larger population of smokers and former smokers without bronchial dysplasia. Eventually, they would like to find out whether this marker could be useful in predicting cancer risk or the outcome of chemopreventive treatment, Chen said.

Aggregation of Cancer Among Relatives of Never Smoking Lung Cancer Patients: Abstract No. 436

First-degree relatives of lung cancer patients who have never smoked are at an increased risk of cancer and are also more likely to be diagnosed with lung cancer, especially at an early age, than first-degree relatives of healthy never-smokers, according to this large study.

“The findings suggest that genetic factors play an important role in lung cancer among never-smokers,” said Olga Gorlova, Ph.D., assistant professor in the Department of Epidemiology at The M.D. Anderson Cancer Center in Houston and lead author of the study.

The researchers compared the number of cancers among first-degree relatives—parents, children, and siblings--of 316 never-smoking lung cancer patients and 318 never-smokers who were healthy. Patients and controls were matched for age, gender, and ethnicity. There were 2,465 first-degree relatives of the patients with lung cancer and 2,441 first-degree relatives of the control group. The median age of cases and controls was about 61 years; two thirds were women and about 80 percent were Caucasian.

The researchers found that the relatives of the lung cancer patients had a 25 percent increased risk of cancer compared to the controls. Offspring had a two-fold higher risk. Mothers of patients had more than double the risk of breast cancer compared to mothers of controls.

The risk of developing cancer at a young age was higher among relatives of never-smoking lung cancer patients. Compared to relatives of controls, their risk of developing lung cancer before age 50 was six times higher, and their risk of any sort of cancer before age 50 was 44 percent higher.

Among the non-smoking relatives of the lung cancer patients the average age of diagnosis of lung cancer was 60.6 years compared to 74.2 years for the non-smoking controls. Among smoking relatives of the patients, there was a nearly 70 percent (1.68) higher risk of lung cancer compared to control relatives.

Gorlova noted that the findings could be useful in counseling family members of people who never smoked and have lung cancer. “Relatives could be aggressively advised to stop smoking or, if lung cancer screening is recommended at some point in the future, this is a high-risk group that could be considered for regular screening,” she said.

The researchers are planning to follow up on this study by investigating genetic factors that appear to underlie the increased cancer incidence in these families.

Cigarette Smoking and Risk of Ovarian Cancer in Scandinavian Women: Abstract No. 4557

Women who smoke or have smoked in the past are at an increased risk of ovarian cancer, according to a large study that has followed more than 100,000 women for over a decade. Up to now, most studies have not shown an association between smoking and ovarian cancer.

“Our study shows consistent results for the association between both current and former smoking and the risk of invasive or borderline ovarian cancer, including different histological subtypes of ovarian cancer,” said Inger T. Gram, M.D., Ph.D., a professor in the Department of Preventive Medicine at the University of Tromsø in Norway and lead author of the study.

The researchers followed more than 100,000 women, who were between 30 and 50 years of age in 1991 and 1992 when they enrolled in the Norwegian-Swedish Cohort Study. A mailed questionnaire completed at the beginning of the study collected data on age at smoking initiation, duration, and number of cigarettes smoked daily. National cancer registries were used to identify members of the cohort who developed ovarian cancer.

By the end of 2003, a total of 312 women had developed either invasive or borderline ovarian cancer. The researchers found that current smokers had a 60 percent (1.60) greater risk of ovarian cancer compared to those who had never smoked at the time of entry into the study. Former smokers had a 50 percent (1.48) higher risk than those who had never smoked. This was after taking into account other possible risk factors, such as age, number of children, menopausal status, oral contraceptive use, and hormone therapy use.

Gram noted that 28 percent of the women were current smokers at study entry. Those who had been smoking for more than 25 years and still were smoking had twice (2.0) the risk of ovarian cancer compared with never smokers.

Plans to follow up on these findings include a study in 300,000 Norwegian women that will look at the associations between smoking and various kinds of cancer, including ovarian cancer.

Given the rising number of women who are beginning to smoke in many countries and the high mortality for ovarian cancers, the findings give teenage girls and adult women yet another reason to avoid smoking or to quit, said Gram.

Second-Hand Smoke Exposure and Survival in Early-Stage, Non-Small Cell Lung Cancer Patients: Abstract No. LB-345

Lung cancer patients who have been exposed to high levels of second-hand smoke do not live as long, on the average, as those with low levels of exposure.

“We know that second-hand smoking increases the risk of lung cancer and studies have suggested that it is associated with lung cancer mortality,” said lead author Wei Zhou, M.D, Ph.D., a Research Scientist at the Harvard School of Public Health in Boston. “But this is the first study to show that second-hand smoking also is associated with lung cancer survival.”

The study included 393 patients with early-stage, non-small cell lung cancer (stages IA - IIB) at the Massachusetts General Hospital. All had their tumors removed surgically, and most had not had any additional therapy. Their median age was 69.

The researchers, led by David C. Christiani, M.D., a professor at Harvard School of Public Health and Harvard Medical School, collected information on the patients’ exposure to second-hand smoke at three different places–work, home, and leisure-time locations, such as restaurants. The questionnaire, administered by an interviewer, collected data on the length of exposure at each location over each patient’s lifetime, before the diagnosis of lung cancer.

Total exposure times were then divided into four quartiles. Patients in the highest quartile had more than 48 years of exposure (the average among the three locations). Those in the lowest quartile had fewer than 28 years’ exposure on average.

After a median of 66 months follow-up from the time of their diagnosis, patients with the least second-hand smoke exposure had the highest survival rates. Moreover, the overall five-year survival rate decreased with increasing exposure: 71 percent of patients with the lowest exposures were alive after five years compared to 61 percent in the next highest quartile, and 49 percent in the third highest. In the highest quartile–those with the highest exposure to second-hand smoke–just 47 percent survived five years.

The association with survival was strong even after accounting for age, gender, stage of cancer, and the patients’ own cigarette smoking over their lifetimes.

Workplace exposure appeared to be the most important factor. Total exposure in the workplace was greater than 42 years for those in the highest exposure group and less than 7 years in the lowest exposure group. The association with both overall survival and relapse-free survival was statistically significant for workplace exposure. The study also showed an association between home and leisure second-hand smoke exposure, but it was not statistically significant.

“The reason for the strong association with workplace exposure may be due both to the length of time people spend at work and the higher levels of smoke they could be exposed to there,” said Zhou.

The researchers now plan to look at survival differences among lung cancer patients who are exposed to second-hand smoke after their diagnosis and at the genetic factors associated with second-hand smoking, smoking, and survival, Zhou 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 60 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.

Contact:

Warren R. Froelich
215/440-9300, Ext. 198
froelich@aacr.org
In Washington, DC (4/1-4/5)
202/249-4004
202/249-4005 fax

Vitamin D and Flavonoids Examined for Impact on Breast and Ovarian Cancers

registration@aacr.org () — Tue, 04 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. - While risk factors for breast and ovarian cancers include menopause, obesity, family history and specific genetic mutations, researchers also are looking at the role of diet in the development, as well as the treatment and prevention of these tumors. At the 97th Annual Meeting of the American Association for Cancer Research, two groups of scientists using sophisticated statistical techniques report their findings of possible preventive properties of Vitamin D against breast cancer. Two other groups of scientists present their work analyzing the possibility that natural antioxidants found in plants, substances called flavonoids, could play a powerful role in preventing both breast and ovarian cancer.

Potential Reduction in Breast Cancer Risk Associated with Vitamin D: Abstract No. 4009

Though scientists have suspected that Vitamin D helps to prevent and possibly even treat breast cancer, population-based studies on the possible link have been few and of limited scope.

Now, new studies by researchers at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto suggest the “sunshine” vitamin may play a significant role in reducing breast cancer risk. The results, based on population data, found the reduction was most apparent among subjects exposed to the highest levels of vitamin D when they were young.

By interviewing about 576 patients who had been diagnosed with breast cancer and 1,135 people who had no cancer, the scientists discovered that significant reductions in breast cancer were found in those who had either worked in an outdoor job, had taken part in outdoor activities when young, or consumed cod liver oil or milk.

Working an outdoor job between ages 10 to 19 resulted in an estimated 40 percent reduced risk of breast cancer, while frequent outdoor activities between ages 10 to 29 lowered breast cancer risk by an estimated 35 percent.

“These outdoor activities included those that didn’t involve physical activity,” said Julie Knight, who headed the Mount Sinai research team. “And so we believe that this is evidence of a reduction of breast cancer risk, associated with earlier exposure to the sun.”

For dietary influences on cancer development, taking cod liver oil between ages 10 to 19 reduced breast cancer risk by about 25 percent, and consuming at least nine glasses of milk every week between the ages of 10 to 29 reduced the risk by 35 percent. The dietary and lifestyle reductions were significant, even when adjusted for other risk factors for breast cancer such as age, ethnicity, close relatives with breast cancer, age at menarche and age at a woman’s first birth.

“What you are exposed to during breast development may be particularly important in determining future breast cancer risk,” Knight said. “Current thinking is that exposures during adolescence or before a full-term pregnancy may have a greater effect, as that is when breast tissue is going through the most rapid development.”

Knight emphasizes that these findings are preliminary estimates of the risk reduction of breast cancer brought about by Vitamin D. The researchers are now looking to solidify these findings, and determine whether physical exercise while outdoors is in any way associated with breast cancer.

Evidence of Need for Increased Vitamin D Fortification of Food Based on Pooled Analysis of Studies of Serum 25-hydroxyvitamin D and Breast cancer: Abstract No. 4008

Increasing doses of dietary Vitamin D may help prevent breast cancer, with the optimal level of intake of Vitamin D more than three times the current average for Americans, according to a study conducted at the University of California, San Diego.

Previous studies have suggested a link between Vitamin D deficiency and higher incidence of breast cancer. Cedric Garland, Dr. P.H., and Edward Gorham, Ph.D., of UCSD, and their colleagues examined existing cancer studies to determine if higher Vitamin D levels in the blood could reduce the risk of cancer.

"There is a strong inverse dose-response relationship between the serum concentration of 25-hydroxyvitamin D and the risk of breast cancer," Garland said. "It's a close fit to a linear model," meaning that higher amounts of 25-hydroxyvitamin D in the serum resulted in decreased risk of breast cancer. The evidence further pointed to a level of Vitamin D measured in blood that correlated with a 50 percent reduction in the incidence of breast cancer.

Garland, Gorham and their colleagues studied a serum Vitamin D metabolite known as 25-hydroxyvitamin D and its association with breast cancer occurrence in a pooled study that included 1,760 women. The studies that provided the data for the pooled analysis were conducted by Elizabeth R. Bertone-Johnson and colleagues at Harvard, and L.C. Lowe and associates at Saint George’s Hospital Medical School in London.

According to the pooled analysis, Vitamin D in blood serum equal to 52 nanograms per milliliter was associated with a 50 percent reduced risk of breast cancer. To move closer to a serum concentration of 52 nanograms/milliliter, a typical individual would have to consume no less than 1,000 International Units (IU) of Vitamin D every day, through supplements or vitamin D-fortified foods. Currently, a typical American consumes only 320 International Units of Vitamin D a day. The upper limit for vitamin D intake established by the National Academy of Sciences is 2,400 IU/day, but no toxic effects of vitamin D intake have been reported for intakes below 3,800 IU per day.

"There is no substantial downside to a serum level of 52 nanograms per milliliter of Vitamin D," said Gorham. "Such levels are common in sunny climates. There is no known adverse effect of serum levels below 160 nanograms per milliliter."

However, since many people use sunscreens and are involved in indoor occupations or shift work, dietary supplements and vitamin D fortified foods are necessary to maintain optimal levels of Vitamin D, the scientists noted.

High intakes of calcium, which could occur with intake of Vitamin D supplements containing calcium, could increase the risk of kidney stones, they warn. However, the dosage level of vitamin D associated with kidney stones in patients far exceeded 3,800 IU/day. Until more studies are completed, the scientists recommended that everyone consume at least 1,000 IU/day of vitamin D3.

Dietary Flavonoid Intake and Breast Cancer Risk among Women in the Long
Island Breast Cancer Study Project: Abstract No. 4014

Flavonoids, a class of antioxidants found in plants, is associated with a reduced risk of breast cancer among post-menopausal women, according to results of the Long Island breast cancer study project. The results are one of the first epidemiologic studies to suggest that these compounds could have a chemoprotective effect among women.

Brian Fink, Susan Steck and Marilie Gammon of the University of North Carolina, Chapel Hill, and other colleagues studied data from a large study of breast cancer incidence and risk factors conducted among women living during the mid-1990s on Long Island, N.Y.

Breast cancer risk was reduced for the highest percentages of total flavonoid intake, compared to the lowest intake of the plant antioxidants. The decreased risk was about 45 percent among post-menopausal women. Risk decreases were not seen in pre-menopausal women. Specific flavonoids -- including flavones, flavan-3-ols and lignans -- were associated with reduced cancer risks ranging from 26 to 39 percent; other flavonoids, such as flavanones, isoflavones and anthocyanidins, showed no relationship with reduced cancer risk.

"These results are consistent with other studies conducted among Mediterranean women," said Fink. "Few epidemiologic studies have examined whether there is a relationship between breast cancer and dietary flavonoids. Our study proposes that dietary flavonoids can help American post-menopausal women reduce their risk of breast cancer."

The researchers examined data from the Long Island study, which was conducted by Dr. Gammon and colleagues between August 1996 and July 1997. The team compared data from 1,434 women with breast cancer to data from 1,440 women who were not diagnosed with the disease.

Flavonols, flavones, lignans and anthocyanidins are all flavonoids, molecules that give plants protection from oxidative damage due to disease and environmental stresses. Flavonoids are classified according to chemical structure, and have been studied for their varying degrees of effectiveness against human diseases, both in treatment and prevention. They are found in green tea, red wine, soybeans, fruit and vegetables.

"There are no recommended dietary standards for ingestion of flavonoids, and we do not know exactly how these chemicals may work on a cellular level," said Fink, whose work was supported with funding from the National Institutes of Health and the Lance Armstrong Foundation. "Minute differences in chemical structure could determine how a certain natural antioxidant may work to prevent disease, including cancer. More study is needed to determine why certain flavonoids appear to be effective at reducing cancer risk, and others do not appear to have these properties."

A Prospective Analysis of Dietary Flavonoid Intake and Epithelial Ovarian Cancer Incidence: Abstract No. 4013

The incidence of ovarian cancer may be reduced with increased consumption of dietary flavonoids, plant chemicals that are found in tea, red wine, fruits and vegetables, according to researchers from Brigham and Women’s Hospital and the Harvard School of Public Health.

The study, conducted by Margaret Gates, a doctoral candidate at the Harvard School of Public Health, looked at food intake surveys and ovarian cancer data from 66,384 participants in the Harvard Nurses' Health Study, which collected health data from 121,700 women over a period of 30 years. “This is the first prospective analysis of flavonoid intake and ovarian cancer incidence,” Gates said.

Gates studied the association between flavonoid intake from food frequency questionnaires completed by the women in 1984, 1990, 1994 and 1998; and 344 confirmed cases of ovarian cancer diagnosed between 1984 and 2002. While there was a significant trend toward decreasing incidence of ovarian cancer with increasing total flavonoid intake, Gates warned that “because this is one of the first studies of the topic, this association needs to be evaluated in another prospective study population before conclusions can be made.”

Gates also analyzed individual flavonoids to evaluate their impact on ovarian cancer incidence. The flavonoid kaempferol, which the nurses consumed primarily from caffeinated tea, broccoli and kale, was associated with decreased ovarian cancer risk. Women with the highest levels of kaempferol intake had a significant 38 percent decrease in ovarian cancer incidence, compared to women with the lowest levels of intake. Two other flavonoids, myricetin and quercetin, showed a possible inverse association with ovarian cancer risk, although the results were largely non-significant.

“The associations were stronger when exposure was defined as cumulative average flavonoid intake over a period of 14 years, which suggests that long-term intake of flavonoids may be important,” Gates said.

But she cautioned that “these findings need to be confirmed by others before any public health recommendations can be made. However, if confirmed, consumption of flavonoids would provide another means for women to decrease their risk of ovarian 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 60 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.

Contact:

Warren R. Froelich
215/440-9300, Ext. 198
froelich@aacr.org
In Washington, DC (4/1-4/5)
202/249-4004
202/249-4005 fax

Molecular Discoveries Aim at Advancing Early Diagnosis of Cancers

registration@aacr.org () — Mon, 03 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. - Molecular messages and signals circulating in blood or contained in cells lining the airway can identify early stage cancer, according to scientists presenting today at the 97th Annual Meeting of the American Association for Cancer Research in Washington, D.C. Researchers have discovered molecular signposts pointing to the presence of cancer, and those signs can provide physicians with early and, in some cases, more specific cancer detection opportunities. The goal of screening and early detection is to identify primary tumors at initial stages of development when they can be successfully controlled or cured with local therapy. Most cancer deaths are caused by metastatic disease, later stage tumors that spread to other sites in the patient. Clinical monitoring of molecular markers of primary tumors and metastasis allows for early response strategies in the treatment to control or cure the disease.

Airway Gene Expression; A Novel Diagnostic Test for Lung Cancer in Smokers: Abstract No. 2420

By piggy-backing a genetic expression assay along with the best available procedure to detect lung cancer, a team of researchers has dramatically improved the sensitivity of diagnosing lung cancer. Moreover, the RNA expression signature from normal epithelial cells of the upper airways in smokers identified three times as many early stage – and more treatable – cancers as did conventional bronchoscopy, according to Avrum Spira, M.D., assistant professor from Boston University Medical Center, and lead author of the study that included scientists from the Lahey Clinic in Burlingham, Mass., and Trinity College in Dublin, Ireland.

The genetic signature of cells from the ‘field of injury’ epithelial cells lining the upper bronchi complemented the clinical bronchoscopy results to identify 95 percent of patients with early or late stage lung cancers. By itself, the genetic signature identified 80 percent of 60 patients who developed lung cancer. Bronchoscopy diagnosed only 53 percent of those patients.

“We are not instituting a new test,” Spira said. “These high-risk patients were suspect for having cancer, and they were already undergoing the bronchoscopy. As part of the bronchoscopy procedure, we took additional samples from a more accessible airway.

“We are adding value to the bronchoscopy exam,” he said. “In the event where the bronchoscopy misses the diagnosis, our test often detects the cancer. Together, the two tests have a very high sensitivity for lung cancer.”

Approximately 300,000 bronchoscopies are performed each year in the United States to diagnose lung cancer. The procedure detects from 30 to 70 percent of all lung cancers, depending on the stage of cancer development.

Where bronchoscopy is weakest, the genetic profiling is strongest, Spira said. Conventional bronchoscopy detected only 30 percent of early, stage one lung cancer in the study’s patient cohort, he reported. The genetic signature picked up 90 percent of those early cancers.

“The genetic signature from the field of injury epithelial cells does really well at the stage of disease that bronchoscopy is doing a poor job,” Spira observed. “Those are the early tumors, and that is the group of patients that if you make the diagnosis at that stage, you are more likely to have a cure with surgery and treatment than if you wait three months and the cancer has a chance to spread.”

The five-year survival rate for people diagnosed with Stage 4 lung cancer is only five percent, Spira noted. Stage 3 survival remains low, averaging less than 20 percent survival after five years.

But with earlier detection while the cancer is still in Stage 1, five-year survival exceeds 60 percent, Spira said.

“The difference is considerable,” he added. “Adding the upper airway harvest of normal epithelial cells to the bronchoscopy procedure enables clinicians to make earlier, more complete diagnosis, and improves the opportunity for successfully treating more lung cancer patients.”

Detection of Blood-Borne Cancer Using Polymerase Chain Reaction for tNOX Messenger RNA: Abstract No. 5684

Cancer cells that circulate in the blood during metastasis carry a cancer-specific protein called tNOX that is generated from an alternate form of tNOX messenger RNA. Scientists now report they can detect this cancer-specific message with cutting-edge molecular technology, researchers from Purdue University reported at the 97th Annual Meeting of the American Association for Cancer Research today.

“Metastatic cancer cells produce the cancer-specific form of the tNOX messenger RNA, and the presence of the alternate message for tNOX in the blood signals the presence of circulating cancer cells in the blood,” said D. James Morre, Ph.D., the Dow Distinguished Professor of Medicinal Chemistry, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana.

By monitoring the levels of a cancer-specific message in blood from 32 patients and 22 healthy volunteers, Morre and colleagues determined that all cancer patients in the study were positive for the presence of an alternate form of tNOX RNA message. None of the cancer-free volunteers or patients with non-cancer disease were detected with the marker.

“Despite the relative small sample size of this study, the assay seems highly correlated with metastatic disease and/or the potential for metastatic disease,” Morre said. He explained that tNOX appears essential to maintain unregulated growth in cancer cells, which is one of the hallmarks of cancer and bolsters the rationale for its use as diagnostic marker.

“tNOX and its constitutive counterpart, CNOX, fulfill an essential role in cell enlargement,” Morre said. “tNOX is translated from a cancer-specific splice variant messenger RNA that is missing exon 4. Both the exon-4-minus mRNA and the mature expressed tNOX protein are specific to cancer and remain undetected in cells or sera from healthy volunteers or patients with diseases other than cancer.”

By harvesting messenger RNA from circulating cells in the blood, Morre and his colleagues were able to amplify the message for tNOX using the reverse transcription polymerase chain reaction. The message was elevated in patients with cancer, but not in healthy individuals or those with non-cancerous diseases.

“Because cells containing the variant tNOX message are shed into the serum, it is a useful pan-cancer marker for clinical metastatic disease,” Morre said. “The test detects circulating cancer cells, and it does have the potential to become a standard screening assay especially for post-operative breast cancer patients to monitor the potential for metastatic spread.” Morre noted that if there was no evidence of metastatic spread post-surgery, patients and their physicians may have the opportunity to circumvent or at least delay the onset of certain chemotherapy strategies until the time that circulating cells appear.

Morre noted that cancer patients participating in the study included breast, lung and ovarian cancers.

“This assay is a promising tool for detecting circulating cancer cells in patients,” Morre said. “It has implications for monitoring tumor progression and therapy in clinical use.”

A Real-Time PCR Test for Septin 9 Gene Methylation Identifies Early Stage Colorectal Cancer in Plasma: Abstract No. LB-224

Free-floating DNA gleaned from blood is a key to early detection of colorectal cancer, according to researchers from the Epigenomics, a molecular diagnostics company.

The researchers found that presence of the methylated form of DNA encoding the so-called Septin 9 gene is found in plasma of up to 57 percent of patients with all stages of colorectal cancer at high levels of specificity (95 percent).

“The presence of methylated Septin 9 DNA in blood is a marker suited as an excellent population screening tool to identify a large number of asymptomatic cancers, and our study is the first of this magnitude and with this level of clinical performance to describe a DNA methylation-based blood test for the early detection of colorectal cancer.” said Catherine Lofton-Day, Ph.D., vice-president, Molecular Biology at Epigenomics.

Lofton-Day noted that a blood-based screening assay will be more patient-friendly than the conventional colorectal cancer screening tool, which requires patients to collect and submit fecal samples for fecal occult blood testing – a considerable obstacle to patient compliance.

While the test to identify methylated Septin 9 DNA in the blood at present is not intended to replace periodic colonoscopy or sigmoidoscopy screening for colon cancer, it can be used more frequently as part of routine yearly physical check-ups to increase the chances of detecting cancer at early stages.

“The test is already better than existing non-invasive early detection methods such as fecal occult blood testing," Lofton-Day said.

Lofton-Day’s findings come from two independent studies that determined Septin 9 levels in a total of 1,500 patients in three distinct categories. One group was known to be free from colon cancer after examination by colonoscopy. A second group included individuals with non-colorectal cancers and other non-cancerous conditions, and a third group consisted of patients with a confirmed diagnosis of colorectal cancer.

In an initial study of 501 samples, 57 percent of colorectal cancers were detected. After validating the Septin 9 assay among the three known-status groups in a set of several hundred samples, Lofton-Day and her colleagues predicted the diagnosis of colorectal cancer in an independent set of 790 patients. In this study the detection rate for all colorectal cancers was 50 percent (104 detected in 209 cases). The false positive rate for both studies was between 4 and 6 percent.

“Different stages of colorectal cancers were detected with similar sensitivity, and detection was not affected by location of the tumor in the colon,” Lofton-Day said. “This is a reliable, non-invasive method to detect many patients with colorectal cancer, but who show little or no symptoms. “

Expression Profiling of Peripheral Blood Cells for the Early Detection of Breast Cancer: Abstract No. 125

A cryptic message may be found in cells circulating in the blood of women – and that cipher may be useful in early diagnosis of breast cancer, according to results from research conducted at the University Clinic at the Norwegian Radium Hospital in collaboration with DiaGenic ASA.

The blood-borne message is read with a genetic expression test to interpret the possible reaction of peripheral blood cells in response to environmental changes in the body due to breast cancer, said Anne-Lise Børresen-Dale, Ph.D., head of the Department of Genetics, Inst. for Cancer Research, DNR, Norway.

“Early detection of breast cancer is the key to optimizing the success of treatment and patient survival,” Børresen-Dale said. “We have identified a gene signature that can discriminate between breast cancer and non-breast cancer in 75 percent of the cases.”

Børresen-Dale and colleagues in partnership with DiaGeneic ASA defined a set of 58 genes that were differentially expressed by peripheral blood cells in the presence or absence of breast cancer. An array platform with 22,000 probes interpreted the blood-borne message from samples of 64 women with breast cancer and 76 women with no sign of the disease. The gene signature correctly predicted the diagnosis of breast cancer in approximately 75 percent of the cases after triple cross validation. The gene signature included genes belonging to similar gene families as the 37 genes identified in the first pilot study performed on filter macroarrays.

In this pilot, published in Breast Cancer Research last year, which included 24 women with breast cancer and 32 controls, the researchers failed to classify cancer in 26 percent of the samples from women diagnosed with breast cancer. The assay also errantly suggested the presence of cancer in 12 percent of samples from cancer-free patients; however, three of the four false positive predictions were from samples donated by healthy women who were pregnant.

“This suggests a possible hormonal effect,” Børresen-Dale commented.

“To be used as a diagnostic tool, we have to increase substantially both sensitivity and specificity, so we indeed have more work to do before any clinical use,” she said. “First we need to sort out if this is specific for breast cancer. And we must analyze whether there is any impact of hormone replacement therapy on the gene signature.

“Furthermore, we aim to determine how early in the development of cancer that this signature indicates the presence of a tumor.

“The first gene signature set that was upregulated in cancer belongs to defense-related genes; genes involved with oxygen stress and immune response. Those genes that were down-regulated in cancer samples are involved with ribosome production and translation and control.”

While the signature was expressed in a woman with ductal carcinoma in situ, indicating that it may be useful in very early stage tumors, it was not evident in a Stage 4 cancer.

“That is probably a systemic disease that has altered the expression profile in the peripheral blood cells very differently,” she said.

Early detection of breast cancer currently relies primarily on mammography, Børresen-Dale noted.

“Mammographic screening has really helped us achieve earlier diagnosis,” Børresen-Dale said. “But it is still not early enough.”

The sensitivity of imaging technology is highly dependent on individual characteristics of the patient’s breast. In a study of more than 11,000 women with no clinical symptoms of breast cancer, mammography detected tumors in 78 percent of all women, but in just 48 percent of women with extremely dense breast tissue. Mammography typically falters at detecting tumors less than 5 millimeters in size, which can be a relatively late stage of tumor development.

“It could really help if a blood sample was taken for gene expression screening at the time the woman had the mammogram done,” Børresen-Dale said. “That may answer discrepancies in the reading and analyzing of the mammogram.”

The use of array technology in the clinical setting generally requires blood sampling and can be performed as part of routine normal health physicals.

“An assay to detect the presence of early stage breast cancer by reading the message made by blood cells in response to cancer can be less demanding on women that need repeated mammography because of uncertain findings, and offers the hope of much earlier detection,” Børresen-Dale said. “That is when the patient has the greatest opportunity for successful treatment options and long term survival.”

# # # #

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 60 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.

Contact:

Russell Vanderboom, Ph.D.
215/440-9300, Ext. 120
vanderboom@aacr.org
In Washington, DC (4/1-4/5)
202/249-4004
202/249-4005 fax

Targeted Therapies Showing Great Promise Against Colorectal Cancer

registration@aacr.org () — Mon, 03 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. − Results from a Phase III study of a new drug show promise for patients with colorectal cancer that has spread to other parts of the body, according to a study presented today during the 97th Annual Meeting of the American Association for Cancer Research.

Investigators have shown that panitumumab improves progression-free survival in patients with metastatic colorectal cancer (mCRC) who had failed standard chemotherapy. In the randomized trial of 463 patients, those who received panitumumab with best supportive care every two weeks (231 pts) showed a 46 percent decrease in the rate of tumor progression or death versus those who received only best supportive care (232 pts). At week 24, approximately four times as many pantimumab patients were alive and progression-free versus those on best-supportive care (18 percent versus five percent). Twice as many panitumumab patients were alive and progression-free at week 32 (10 percent versus four percent).

Study investigators also reported that panitumumab significantly improved disease control. In patients who responded, the median duration of response was 17 weeks. Extended follow-up also revealed that even after 32 weeks, a larger percentage of patients in the panitumumab with best supportive care group were alive without progression than in the group assigned to best supportive care alone.

"We are encouraged by these results, particularly that panitumumab was well-tolerated in patients with metastatic colorectal cancer, with very few major adverse reactions," said Marc Peeters, M.D., Ph.D., coordinator of the Digestive Oncology Unit, from Ghent University Hospital in Belgium.

Recently, researchers have begun to focus their efforts on developing cancer therapies that are not only effective, but also are easier on the body than current therapies. Using newer therapies that are derived from human protein sequences, investigators are finding that the body is less likely to develop side effects from these drugs, such as allergic reactions.

Panitumumab is the first fully human monoclonal antibody that targets the epidermal growth factor receptor (EGFr), a protein that plays an important role in cancer cell signaling. EGFr activates when naturally occurring proteins in the body, such as epidermal growth factor (EGF), bind to it and trigger signals to encourage cell growth.

Panitumumab binds to EGFr, preventing the natural protein from binding to it and interfering with the signals that would otherwise stimulate growth of the cancer cell and allow it to survive.

“Studies involving the use of panitumumab alone and in combination with other therapies for various cancers may confirm that the use of human monoclonal antibodies is a great step forward to effectively treat cancer,” said Dr. Peeters.

The most common side effect was rash, and other lesser side effects included fatigue, nausea and diarrhea. No anti-drug antibody formation was observed.

*Abstract No. CP-1: A Phase 3, Multicenter, Randomized Controlled Trial (RCT) of Panitumumab Plus Best Supportive Care (BSC) vs. BSC Alone in Patients (pts) with Metastatic Colorectal Cancer (mCRC)

# # # #

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 60 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.

Contact:

Warren Froelich/AACR
froelich@aacr.org
215/440-9300, Ext. 198
In Washington, DC: (4/1– 4/5)
202/249-4004
202-249-4005 fax

Researchers Seek Alternative for Leukemia Patients Resistant to Standard Therapies

registration@aacr.org () — Mon, 03 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. – A study led by researchers from the Howard Hughes Medical Institute has found that dasatinib provides significant benefit in chronic myeloid leukemia (CML) patients resistant to Gleevec® (imatinib), according to a study presented today during the 97th Annual Meeting of the American Association for Cancer Research.

In an update of a phase I study initiated in November 2003, researchers looked at the use of dasatinib in imatinib resistant or intolerant patients with CML in late chronic phase (CP), accelerated phase (AP), myeloid blast crisis (MBC), or lymphoid blast crisis (LBC/Ph+ ALL). Data are available for 84 patients (40 CP, 11 AP, 23 MBC, 10 LBC/Ph+ ALL). A blast crisis is the progression of diseases to an acute advanced phase.

Imatinib – which blocks the irregular protein that allows the overproduction of abnormal white blood cells – has become a standard therapy for CML patients not undergoing stem cell transplantation. However, a number of patients have developed resistance to this treatment because their cancer cells are able to mutate and adapt.

The 40 CP patients, with five years median duration of CML, were treated with 15 to 180 mg of dasatinib either once daily (QD) or twice daily (BID) for a median of 13 months. The rate of complete hematologic response (CHR) in CP patients was 93 percent, while major cytogenetic responses (MCyR) were observed in 45 percent and complete cytogenetic response (CCyR) in 35 percent.

In advanced disease, 44 patients have been treated with dasatinib (50 to 240 mg BID) for a median of 37 months. The rate of major hematologic response (MHR) is 81 percent in AP, 61 percent in MBC, and 80 percent in LBC/Ph+ ALL. The overall rates of MCyR and CCyR in advanced disease were 43 percent and 25 percent, respectively. Responses were durable in CP and AP patients, but relapses have occurred in the MBC and LBC/Ph+ ALL groups, often due to dasatinib-resistant BCR-ABL mutations.

CML is usually diagnosed by finding what is called the Philadelphia chromosome (Ph chromosome). The Ph chromosome is the result of a genetic abnormality among portions of chromosomes 9 and 22. In this, part of the BCR (breakpoint cluster region) gene from chromosome 22 is merged with part of the ABL (abelson leukemia virus) gene on chromosome 9. The irregularity takes place in a single bone marrow cell and – through the process of cell division and expansion – results in leukemia, including some cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Imatinib resistance in CML and Ph chromosome positive ALL is frequently associated with BCR-ABL mutations that interfere with the ability of imatinib to stop BCR-ABL overproduction. Dasatinib (BMS-354825), which targets BCR-ABL, is 325-fold stronger than imatinib in cells with normal BCR-ABL genes and has demonstrated preclinical activity against 18 of 19 imatinib-resistant BCR-ABL mutants.

*Abstract No. CP-2: Development of the ABL Kinase Inhibitor, Dasatinib (BMS-354825), in Imatinib-Resistant Philadelphia Chromosome Positive Leukemias

# # # #

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 60 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.

Contact:

Warren Froelich/AACR
froelich@aacr.org
215/440-9300, Ext. 198
In Washington, DC: (4/1– 4/5)
202/249-4004
202-249-4005 fax

Studies Confirm Celecoxib May Help Prevent Colorectal Cancer In High Risk Patients

registration@aacr.org () — Mon, 03 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. – During the past year, the study of the potential use of COX-2 (cyclooxygenase-2) inhibitors to prevent colorectal and breast cancer has come under intense scrutiny. Recent research questioned the safety of these medicines as pain relievers, which was the initial indication, as well as for chemoprevention of cancer. Now, the latest data show that COX-2 inhibitors are highly effective in preventing pre-malignant tumors of the colon, and therefore may be useful in preventing colorectal cancer among high-risk patients.

According to two studies presented today at the 97th Annual Meeting of the American Association for Cancer Research, the over-expression of the COX-2 enzyme is related to the growth and spread of colorectal tumors. COX-2 inhibitors may reduce the occurrence of the precursor, colorectal adenomas (benign tumors) in patients with a family history of the disease, as well as the development of sporadic colorectal tumors.

Celecoxib reduces sporadic colorectal adenomas: Results from the Adenoma Prevention with Celecoxib (APC) trial: Abstract No. CP-3

Investigators from the Adenoma Prevention with Celecoxib Study (APC) enrolled 2,035 patients to a randomized, double-blind trial of the COX-2 inhibitor, celecoxib (Celebrex®), to prevent colorectal adenomas. Results of the study revealed that celecoxib significantly reduced the formation of large intestinal adenomas during a 3-year period after removal of polyps in patients at high risk of developing colorectal cancer.

Of the participants, 679 patients received a placebo, 685 patients received 200 mg of celecoxib and 671 patients received 400 mg of celecoxib, administered twice daily. The randomization of this trial took into consideration the use of low dose aspirin in 31 percent of participants. A follow-up colonoscopy was conducted in 89 percent of participants after one year and 76 percent received a follow-up colonoscopy at three years.

The incidence of one or more benign tumors during colonoscopy was 61 percent in those taking placebo; in patients taking celecoxib this percentage was reduced by 45 percent (p<0.0001). The relative risk of advanced neoplasms (tumor) with adenomas more than one centimeter in diameter or with tubulovillous or villous features (premalignant rectal polyps), severe dysplasia (abnormal growth) or invasive cancer were also drastically reduced in patients using celecoxib, with 66 percent fewer tumors in these patients (p<0.0001).

“The results of this study show that patients at risk for developing colorectal cancer have dramatically fewer pre-malignant tumors when they take celecoxib,” said Monica Bertagnolli, M.D., associate professor of surgery, Harvard University, Boston, Mass.

“This work shows that drugs that inhibit COX-2 activity are important tools in developing effective preventive therapies for colorectal cancer,” she said.

Chemoprevention of Colorectal Adenomas With Celecoxib in an International Randomized, Placebo-Controlled, Double-Blind Trial: Abstract No. CP-3

A prior study has shown that administration of the COX-2 inhibitor, celecoxib, is associated with a reduction in colorectal adenoma size and number in familial adenomatous polyposis (FAP). Therefore, researchers in the Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) with Celecoxib Trial tested the effectiveness of celecoxib in reducing the incidence of sporadic colorectal adenomas.

The PreSAP study was a randomized, double-blind, placebo-controlled study enrolling 1,561 patients at 107 sites in 32 countries. PreSAP researchers hoped to determine the effectiveness of taking 400 mg celecoxib once daily to reduce the number of patients with new adenomas and the grade, size and number of new adenomas.

The trial started in March 2001 with patients who had undergone removal of all colorectal polyps, known as a polypectomy. Patients were excluded if they had FAP, hereditary nonpolyposis colorectal cancer (with an absence of polyps) or a history of inflammatory bowel disease. During the trial, patients did not take nonsteroidal anti-inflammatory drugs (NSAIDs) except cardioprotective doses of aspirin.

“Results of our study showed that celecoxib holds great promise for the prevention of cancer,” said Nadir Arber, M.D., M.Sc., Head, Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Israel. “For patients at high-risk of developing colorectal cancer, celecoxib may be considered while weighing the risk of potential cardiovascular events.”

Patients were split into a 3:2 ratio of celecoxib and placebo and divided by baseline aspirin use (17 percent, placebo; 16.6 percent celecoxib) or non-use (83 percent placebo; 83.4 percent celecoxib); 933 patients received celecoxib and 628 received placebo. Of the total patients, 88.7 percent underwent a colonoscopy with or without removal of polyps at one year and 79.2 percent at year three.

The administration of celecoxib was stopped after the Adenoma Prevention with Celecoxib (APC) study found at 33 months a two-to-three-fold increase in serious adverse cardiovascular events. PreSAP data at the time of the APC announcement indicated a hazard ratio of 1.2 for those taking celecoxib compared with placebo for death from cardiovascular events and nonfatal heart attack or stroke.

The incidence of adenomas at year three was 49.3 percent in the placebo group, but significantly lower in the group taking celecoxib (p<0.0001). In high-risk patients, the recurrence was also greatly reduced (p=0.0002). The prevalence of adverse events was similar in both the placebo (74 percent) and celecoxib groups (76.8 percent), although patients taking celecoxib had a higher risk of cardiovascular events than those taking placebo (7.5 percent versus 4.6 percent).

Said Dr. Arber, “Research has shown that in order to reduce incidence of cancer, we need to develop better prevention methods for those at highest risk of developing the disease.

“We are encouraged by these results and hope the data from both the APC and PreSAP trials lead to the continuation and implementation of additional clinical trials with COX-2 inhibitors for the prevention of colorectal and other cancers, such as breast. Understanding the molecular mechanisms by which these compounds work is another important scientific goal.”

# # # #

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 60 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.

Contact:

Warren R. Froelich
215/440-9300, Ext. 198
froelich@aacr.org
In Washington, DC (4/1-4/5)
202/249-4004
202/249-4005 fax

Racial Disparities in Cancer Not as Simple as Black and White

registration@aacr.org () — Sun, 02 Apr 2006 12:00:00 GMT

WASHINGTON, D.C. -- African-Americans are more likely to develop cancer and to die from this disease than any other racial or ethnic group in the U.S. population. The cancer death rate among African-America men is 40 percent higher than that of white men; it is 14 percent higher in black women. Possible causes for this discrepancy include lack of health insurance, poverty, language and cultural barriers, and inadequate access to early detection services and good medical care. Research reported today at the 97th 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 and whites.

Underserved African-American and White Women with Breast Cancer Have Similar Prognostic Profiles for Estrogen Receptor and Tumor Grade: Abstract No. 3696

The racial disparity in breast cancer prognosis and survival may have more to do with socioeconomic status, rather than biological factors, according to a study of women diagnosed and treated at a public hospital. Though the population sample was relatively small, including 341 African-American and 94 white women, the results suggest that low economic standing contributes to similarly poor prognostic profiles for tumor grade and estrogen receptor status in both races, according to the researchers.

“This is the first study of its kind in the U.S. based on data from a single institution,” said Keith A. Dookeran, M.B.B.S, FRCS (Ed), leader of the research team at the Minority-Based-Community Clinical Oncology Program at Stroger Hospital of Cook County. “Most of the other studies of the apparent difference in breast cancer prognosis between African-American and white women drew on data from many different geographic areas.”

When Dookeran and his team narrowed the study population to patients at a single, public institution, and adjusted the data for age and stage of disease, they found no significant difference in tumor grade or estrogen receptor status between white and African-American women.

“Cook County Hospital is a public hospital,” Dookeran said. “The women here are largely uninsured and of low socioeconomic status, and they appear to have similar prognostic indicators with high-grade and ER-negative tumors, be they African-American or white.”

“Our results suggest that low socioeconomic status, regardless of race, is associated with a particular tumor phenotype.” Other research attributes the poorer prognosis for breast cancer in African-American women, compared to white women, to the more frequent occurrence in blacks of high-grade, estrogen receptor negative tumors that hinder treatment options.

High-grade- and estrogen receptor-negative tumors signal an aggressive breast cancer with a lower rate of survivability. Estrogen receptor-negative tumors are so called because they do not express the genes that bind to estrogen, the hormone which plays a crucial role in the development and progression of the disease. Some of the most effective chemotherapy treatments for breast cancer act by targeting the receptors and inhibiting their ability to stimulate estrogen production in the breast.

Dookeran and his colleagues at the NCI-supported Minority-Based-Community Clinical Oncology Program at Stroger Hospital wondered whether there really is a connection between race and breast tumor biology when all the other variables were factored into the inequity equation, such as, access to preventative care and diagnostic testing; availability of health insurance; socioeconomic standing; and geographic location.

“African-American women are more commonly underserved and have low socioeconomic status (SES), and other studies suggest that SES, not simply race, is associated with this prognostic profile,” said Dookeran.

To assure a consistent standard of diagnosis and a common quality of care, Dr. Dookeran and his colleagues studied only women from the Minority-Based-Community Clinical Oncology Program at Stroger Hospital. After adjusting for age, the researchers found no significant differences between races regarding stage, ER status and tumor grade. Furthermore, disease-free, distant disease-free and overall survival were similar for both races overall, and also for ER positive subsets.

Black-white Disparities in the Recommendation and Outcomes of Adjuvant Chemotherapy Among Colorectal Cancer Patients: Abstract No. 659

Chemotherapy is recommended to treat colorectal cancer (CRC) in whites more often than in African-Americans, according to a study of more than 17,000 CRC patients of both races in Alabama.

Hanaa S. Elhefni, M.D., M.S, M.P.H., of the Wright State University in Dayton, Ohio, studied the disparity in CRC mortality rates between African-Americans and whites. According to the U.S. Centers for Disease Control and Prevention, while the five-year survival rate for whites with the disease rose to 64 percent over the last 25 years, the rate for African-Americans improved to just 55 percent during the same period.

“This disparity could be partly attributed to differences in risk factors,” Elhefni said, “but variations in medical practice may also be potential contributors.”

The study investigated patterns and trends in adjuvant chemotherapy recommendations, use and outcomes for all black and white CRC patients diagnosed between 1996 and 2002 in Alabama. Adjusting for potential confounding variables such as age, sex and stage of disease at diagnosis, Elhefni found that blacks were 20 percent less likely to have chemotherapy recommended than whites. The compliance rate for blacks and whites prescribed chemotherapy was the same.

Both African-Americans and whites benefit significantly from adjuvant chemotherapy for CRC. Five-year survival rates were significantly higher and mortality rates significantly lower among all those who received the treatment, compared to those who did not.

“Obviously, the disparity in CRC outcomes could be greatly reduced by changes in medical practice,” Elhefni said. “But it is a complex situation, not a simple matter of racial bias. More studies are necessary to identify the factors that influence physician and patient choices when faced with cancer, and to find the best ways to narrow the management/treatment and mortality gaps between the races.”

The Relation of Overall and Central Obesity to Risk of Breast Cancer in African-American Women: Abstract No. 2024

Contrary to long-held theory, obesity may not increase the risk of breast cancer among older African-American women, according to research performed at Boston University and Howard University in Washington, D.C.

However, the study confirmed previous work that younger women with a high body mass index (BMI) have a reduced risk of breast cancer. The research team, led by Julie R. Palmer, Sc.D., professor of epidemiology at the Boston University School of Public Health, focused on the relationship between breast cancer and various measures of obesity in African-American women, in particular, because the prevalence of obesity in the U.S. is highest in the black population.

There is also a tremendous amount of information available from the Black Women’s Health study, which enrolled 59,000 participants in 1995, and followed up on the health and medical status of each with biennial questionnaires.

After eight years of follow-up, 809 women reported having breast cancer—about half of them premenopausal and half postmenopausal. Whether a breast cancer occurs before or after menopause is an important consideration in light of the association between estrogen-fueled breast cell proliferation and the development and progression of breast cancer Palmer’s group confirmed the findings of previous studies that a higher BMI at age 18 decreases a woman’s risk of developing premenopausal breast cancer and, possibly, postmenopausal breast cancer as well.

“Some previous research, but not all, has shown that high body mass index among older women increases breast cancer risk,” Palmer explained. “We actually found the opposite in our study. African-American women with a BMI that qualifies them as obese did not have a higher risk of getting breast cancer. In fact, the risk was slightly lower in obese women overall, in agreement with findings from another study of black women.”

One possible explanation for the discrepancy between the findings for black and white women has to do with differences in the timing of excess weight gain, with black women, in general, becoming overweight at younger ages than white women. There is some evidence that the adverse effect of overweight on postmenopausal breast cancer risk is strongest in the decades closely following the weight gain. Indeed, in Palmer’s study, while there was no increased risk with current BMI overall, there was an association between increasing risk and increasing BMI among postmenopausal women under age 50. Their breast cancer would have developed most closely in time to their maximum weight gain.

The latest report from the American Cancer Society states that the overall rate of breast cancer is 17 percent lower in African-American women than in white women, but the five-year survival rate is 14 percent higher in blacks.

Noting the health benefits of maintaining an optimum weight, Palmer points out that her research does not change that message. “The study results may help explain why breast cancer incidence is lower in black women than white women after age 50 even though the prevalence of obesity is higher,” she said.

Racial Differences in Triple Negative Breast Tumors Among Women in Atlanta: Abstract No. LB-4

They’re commonly referred to as “triple negatives”— breast cancers characterized by three biological components that make the disease more difficult to treat. Oncologists base treatment decisions on the presence of three hormones known to fuel most breast cancers—estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2, or HER2. The most effective chemotherapy agents for breast cancer, such as tamoxifen and trastuzumab (Herceptin), work by targeting these hormones. Women with triple negative tumors lack all three.

In a study of racial differences in the prevalence of triple negative invasive breast tumors, a team of researchers from Emory University in Atlanta, the Fred Hutchinson Cancer Research Center in Seattle, and the Centers for Disease Control, found the incidence of triple negative disease in African-American women to be more than twice that of white women.

“Triple negative disease has not been adequately described or studied, particularly among minority populations,” said Emory researcher Mary Jo Lund, Ph.D. “It has the worst prognosis because the tumors have the worst characteristics and preclude the use of the most common, effective treatments,” said Lund.

To assess the racial differences in the prevalence of triple negative breast cancer, Lund and her colleagues in Atlanta analyzed tumor data from Fred Hutchinson Cancer Research Center collaborator Peggy Porter, M.D., and data from their study of racial differences in progression of breast cancer among Atlanta women under the age of 55.

When the data were broken down by race and adjusted for age and stage of disease at the time of diagnosis, the team found that 47 percent of tumors in black women were negative for estrogen receptor, progesterone receptor, and HER2, compared to 22 percent in whites. There also were strong associations found in African-American women and white women between triple negative disease and high-grade tumors and abnormal expression of p53, a tumor-suppressor gene with cancer-inhibiting properties.

At all ages, African-American women are at lower risk for breast cancer compared to white women. However, for women under the age of 50, African-American women are at increased risk over white women of the same age. “There is also evidence that younger African-American women have breast tumors with more aggressive features,” said Porter.

“Additional studies are needed to examine the risk factors for triple negative tumors, and why black women have this increased risk,” said Lund. “Our results are provocative and carry the message that African-American women might be at higher risk for worse breast tumors and at an earlier age.”

# # # #

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 60 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.

Contact:

Elizabeth Tait
215-440-9300 ext. 144
tait@aacr.org
In Washington 4/1-4/5
202-249-4004 (phone)
202-249-4005 (fax)

Funding for, and Societal Impact of, Cancer Research to Be Discussed

registration@aacr.org () — Tue, 28 Mar 2006 12:00:00 GMT

WASHINGTON, D.C. – During the past few months, funding for cancer research has received some bad news. In December 2005, the President signed the final appropriations bill for fiscal year 2006, which provided $31 million less for cancer research than the year before. This was the first hard cut since the passage of the National Cancer Act in 1971. More recently, the President announced his proposed budget for fiscal year 2007 – it slashes an additional $40 million from the already reduced 2006 funding level.

As a result, the cancer research community is bracing for a major shift in the number of scientists in the field and, consequently, the speed of advances needed to prevent and cure this disease.

For example, federal funding cuts likely will deter young investigators, meaning fewer drugs for development and application in the future. Meanwhile, other nations are increasing research funding, with the likelihood that some of the top investigators in the U.S. will be drawn overseas, eroding this nation’s competitive advantage in this field.

The cuts come at a time when deaths from cancer are falling for the first time in 70 years, according to recent reports from the National Center for Health Statistics. Declining death rates clearly stem from research advances in the early diagnosis and treatment of a variety of tumors. Overall, cancer survivorship has increased from 30 percent in the early 1970s to 64 percent today. The statistics are even better for those diagnosed before the age of 65, with roughly seven out of every 10 surviving their disease in this age group. But funding cuts will put a brake on future progress, resulting in fewer lives saved through research.

In a press briefing scheduled for 2:15 p.m., Tuesday, April 4 at the Washington Convention Center, leading cancer researchers and advocates will discuss the implications of funding cuts for cancer research. An economist from the University of Chicago also will reveal the results of a new study about the economic and societal impacts of improved longevity and health resulting from cancer research. The briefing will take place during the 97th Annual Meeting of the American Association for Cancer Research (AACR).

Invited speakers will include:

Peter Jones, Ph.D., D.Sc., president of the AACR, and Director of the University of Southern California/Norris Comprehensive Cancer Center and Distinguished Professor of Biochemistry and Molecular Biology, and Urology at the Keck School of Medicine at USC.

William G. Nelson V, M.D., Ph.D., professor of oncology, urology, pharmacology, medicine & pathology at Johns Hopkins University School of Medicine and chairperson of the AACR Science Policy & Legislative Affairs Committee

Mary Jackson Scroggins, M.A., co-founder and president of In My Sister’s Care, and member of the National Cancer Institute’s Director’s Consumer Liaison Group and of the Board of Directors of the Ovarian Cancer National Alliance

Julie Fleshman, J.D., M.B.A., president and CEO of PanCan

Kevin M. Murphy, Ph.D., George J. Stigler Distinguished Service Professor of Economics at the University of Chicago Graduate School of Business

# # # #

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 60 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.

Contact:

Warren Froelich/AACR
215/440-9300 ext. 198
froelich@aacr.org
In Washington, DC (4/1-4/5)
202/249-4004
202/249-4005 fax

International Scientists, Physicians Assemble at the American Association for Cancer Research Annual Meeting to Discuss Latest Advances

registration@aacr.org () — Tue, 28 Mar 2006 12:00:00 GMT

WASHINGTON, D.C. − World-renowned scientists, physicians, academicians and advocates will gather for the 97th Annual Meeting of the American Association for Cancer Research (AACR), taking place April 1-5 at the Washington Convention Center, Washington, D.C. About 16,000 attendees from around the world are expected at this year’s meeting where presentations will focus on the latest cutting-edge findings in laboratory, translational and clinical cancer research.

“We are at a critical juncture in the field of cancer research and the exchange of scientific information has taken on a greater urgency,” said Peter A. Jones, Ph.D., D.Sc., president of the AACR. “With pending cuts to the research budget of the National Institutes of Health, and specifically the National Cancer Institute, the free-flow of information shared amongst researchers and oncologists at the AACR Annual Meeting has never played a greater role in advancing the field.”

This year’s Annual Meeting will focus on new and promising therapeutic approaches for the prevention and treatment of cancer, and will highlight data from all stages of the research spectrum – from early stage basic research through late-stage clinical trial results. The opening plenary session, “Looking into the Future of Cancer Therapy,” will feature world leaders in the fields of cancer genetics, molecular diagnostics, chemistry, imaging, clinical research, and stem cell biology.

Additionally, a special clinical plenary session, “Breakthroughs in Clinical Research,” will be offered for the first time at AACR. During this session, investigators will discuss major breaking news about late-phase clinical trials, highlighting the science that led up to the trials and new data with direct clinical impact.

“We believe that the accelerating pace of cancer research discoveries is unprecedented and will lead to opportunities for more effective treatment of many forms of cancer. The rapid progress in our understanding of different types of cancer at the molecular level is now starting to bear fruit and it will have a very significant impact in our ability to treat and hopefully prevent these diseases,” said Daniel A. Haber, M.D., Ph.D., scientific chairperson of the 2006 AACR Program Committee.

“Research presented during the AACR Annual Meeting allows us to link together the latest advances in laboratory research in molecular biology, genetics and chemistry, with discoveries in public health and population science, and recent breakthroughs in clinical research. Through its exceptional scope, the Meeting will offer a broad view of recent progress in cancer research, as well as an array of novel findings, from molecular pathways to technological devices, diagnostic tools, strategies for reducing cancer risk, and developing new therapeutic approaches.”

AACR’s Annual Meeting attracts attendees including leading industry, academic 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 formulations of new collaborations. This year, more than 6,100 abstracts were submitted for presentation, complementing an outstanding program of scientific and educational events already scheduled.

Other meeting highlights include:

Press briefings: COX-2 inhibitors for cancer prevention; panitumumab for treatment of colorectal cancer; health disparities in cancer care and etiology; early diagnosis of cancer; latest on diet for cancer prevention; effects of smoking on cancer patients; significance of infection and inflammation on cancer incidence; novel, early stage drug studies; prognostic outcomes for cancer; impact of funding on cancer research and patients.
Symposia and Forums: covering a diverse range of timely and central topics of critical interest to the broad cancer community, as well as state-of-the-art cancer research development reviews.

# # # #

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 60 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.

Contact:

Warren Froelich/AACR
215/440-9300 ext. 198
froelich@aacr.org
In Washington, DC (4/1-4/5)
202/249-4004
202/249-4005 fax

Bernard Fisher Receives American Association for Cancer Research Lifetime Achievement Award

registration@aacr.org () — Mon, 27 Mar 2006 12:00:00 GMT

PHILADELPHIA – Bernard Fisher, M.D., the renowned clinical cancer researcher whose career has been dedicated toward improving survival as well as quality of life for women with breast cancer, will receive the American Association for Cancer Research Award for Lifetime Achievement in Cancer Research.

The award will be presented April 2 during ceremonies at AACR’s 97th Annual Meeting in Washington, D.C.

Dr. Fisher ‘s early work on tumor metastasis paved the way for later hypotheses about the spread of this disease. He used clinical trials to confirm that patterns of tumor spread are not solely dictated by anatomical considerations, but are also influenced by intrinsic factors in the tumor cells and the organs they invade.

Dr. Fisher’s systematic clinical trials changed the way physicians manage patients with breast cancer. Together with a consortium of colleagues, he evaluated the effect of radical surgical procedures for breast cancer and found that radical mastectomy was no more effective than total mastectomy. Further investigations revealed that a combination of lumpectomy and radiation therapy was equally effective as total mastectomy.

Dr. Fisher and his colleagues also were instrumental in defining the effectiveness of adjuvant chemotherapy and hormonal therapy with the synthetic estrogen tamoxifen in treating breast cancer as a systemic disease. His studies revealed that tamoxifen substantially reduces the incidence of breast cancer in high-risk women when taken as a preventative measure.

“Dr. Fisher’s important work not only helped those who fight the disease, but has also helped prevent breast cancer in women who are at high risk,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “We are honored to recognize Dr. Fisher’s exemplary contributions to the field of breast cancer research and improvement in the quality of life for women who struggle with this disease.”

Dr. Fisher is a 1943 graduate of the University of Pittsburgh School of Medicine, where he spent the majority of his career. From 1950 through 1952, he was a fellow in experimental surgery at the University of Pennsylvania, and, in 1955, he served as a research fellow at the London-Post-Graduate Medical School. In 1959, Dr. Fisher became professor of surgery at the University of Pittsburgh, and, in 1986, was appointed Distinguished Service Professor of Surgery at the university. Dr. Fisher co-founded the National Surgical Adjuvant Breast and Bowel Project, a research consortium which he chaired from 1967 to 1994. In his role as past chairman and scientific director of that Pittsburgh-based research consortium, Dr. Fisher and his colleagues contributed research that set a new course not only for the treatment of breast cancer but for other types of cancer as well.

Dr. Fisher’s previous honors and awards include the Albert Lasker Clinical Medical Research Award, the General Motors Cancer Research Foundation’s Kettering Prize, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the American Cancer Society Medal of Honor, and the AACR-Joseph H. Burchenal Clinical Research Award.

The AACR Award for Lifetime Achievement in Cancer Research was established and first presented in 2004 to honor individuals who have made significant fundamental contributions to cancer researcher 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 understanding, controlling or curing cancer, and the improvement of the human condition for those who have the 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 more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 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.

Contact:

Russell Vanderboom, Ph.D.
215-440-9300 ext. 120
vanderboom@aacr.org

Sherry Lansing and Janet Woodcock Receive AACR Public Service Awards

registration@aacr.org () — Mon, 27 Mar 2006 12:00:00 GMT

WASHINGTON, D.C. -- Each year at its Annual Meeting, the American Association for Cancer Research gives special recognition to distinguished individuals whose efforts and dedication have helped to increase awareness about the importance of cancer research.

The recipients of this year’s Public Service Awards are Sherry Lansing, former Chairman and CEO of the Motion Picture Group Paramount Pictures; and Janet Woodcock, M.D., deputy commissioner for operations and chief operating officer at the U.S. Food and Drug Administration. Their awards will be presented during a special ceremony chaired by AACR’s president, Peter A. Jones, Ph.D., D.S.c.

Sherry Lansing began her career in Hollywood as a model and actress before becoming the first woman to run a major motion picture studio. During her tenure at Paramount, the studio released such major films as Forrest Gump and Saving Private Ryan. More recently, Lansing has turned her focus to philanthropy. Through her leadership as chairperson of the nonprofit advocacy and fundraising group, Stop Cancer, she has raised millions of dollars for cancer research, and is active on the Board of Friends of Cancer Research. In 2005, she was appointed to the Independent Citizen’s Oversight Committee, which directs California’s stem cell research program, and was elected to the Board of Trustees of the AACR Foundation. She also established the Sherry Lansing Foundation to concentrate on health, education, and cancer research.

Janet Woodcock, M.D., who has been with the FDA since 1986, is being recognized for her pivotal leadership role in streamlining and reorganizing the agency’s oversight of cancer medicines through the creation of the new Office of Oncology Drug Products. She introduced the concept of pharmaceutical risk management in 2000 and her leadership of the “Pharmaceutical Quality for the 21st Century Initiative” has modernized pharmaceutical manufacturing and agency-industry interactions. Further, her skillful role in spearheading the FDA’s “Critical Path Initiative” is being recognized for its potential in bringing outstanding science to the consideration of new cancer therapeutics, preventives, and diagnostics. Such work holds the promise of eliminating barriers, enhancing safety, and accelerating the delivery of these life-saving vehicles. The awards ceremony will take place at 8:00 a.m. on Sunday, April 2, 2006, in Hall D of the Washington Convention Center. Members of the media are welcome to attend.

Editors Note: Photographs of Ms. Lansing and Dr. Woodcock are available upon request

# # # #

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 60 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.

Contact:

Angela DeCicco
215-440-9300 ext. 104
decicco@aacr.org

Scientists Making Advances in Cancer Prevention, Detection and Treatment to Receive International Awards

registration@aacr.org () — Fri, 24 Mar 2006 12:00:00 GMT

AACR Confers Honors at 97th Annual Meeting

PHILADELPHIA — Leading scientists whose work in research laboratories, universities and medical centers is helping to understand and eradicate cancer will be recognized April 1-5, 2006, by the American Association for Cancer Research (AACR) at its 97th Annual Meeting in Washington, D.C.

A series of awards is given annually by the AACR – the world's oldest and largest professional society representing cancer scientists from the United States and more than 60 other countries – to honor world-class accomplishments in basic research, clinical care, therapeutics and prevention. Each recipient presents a lecture at the AACR Annual Meeting.

“We are privileged to acknowledge just a few of the extraordinary men and women who, over the years, have given us a clear understanding of how cancer evolves and of the signals that drive and nourish its growth and spread, and those who have improved patient care and preventive strategies,” said Margaret Foti, Ph.D., M.D. (h.c.), AACR chief executive officer.

“This is an exciting time in cancer research, and the AACR award winners are among the leaders in this new era of discovery, therapeutics, and treatment,” she added.

Each award has its own selection committee composed of members of the AACR. Peers and colleagues nominate the award candidates.

This year’s winners are:

Carlo M. Croce, M.D., The John Wolfe Professor for Cancer Research, Chairman, Department of Molecular Virology, Immunology, and Medical Genetics, Director, Human Cancer Genetics Program at The Ohio State University Comprehensive Cancer Center in Columbus, will receive the 46th AACR-G.H.A. Clowes Memorial Award for his seminal contributions that revolutionized leukemia and lymphoma research and treatment. The AACR and Eli Lilly and Company established this award in 1961 to honor Dr. Clowes, a founding member of AACR and a research director at Eli Lilly. The award – the oldest given by AACR – recognizes an individual with outstanding recent accomplishments in basic cancer research. Dr. Croce’s lecture, “Roles of microRNA Genes in Leukemogenesis,” will take place at 9:00 a.m. on Tuesday, April 4, in Hall D of the Washington Convention Center.

Wiliam G. Kaelin, Jr., M.D., Investigator, Howard Hughes Medical Institute, and Professor of Medicine, Dana-Farber Cancer Institute and Brigham & Women’s Hospital, Harvard Medical School, Boston, Mass., will be awarded the 30th AACR-Richard and Hinda Rosenthal Foundation Award. The Rosenthal Foundation, built on the belief that those who reap unusual benefits from society have an obligation to repay the debt with creative and energetic contributions to human progress, founded the award with the AACR in 1977 to recognize research that has made, or promises to soon make, a notable contribution to improved clinical care in the field of cancer, and to provide incentive to such young investigators relatively early in their careers. Dr. Kaelin, who is honored for his discoveries related to the von Hippel-Lindau tumor suppressor protein (pVHL), will give his lecture “The von Hippel-Lindau Hereditary Cancer Syndrome: Insights into Oxygen Sensing and Cancer,” at noon on Tuesday, April 4, in Hall D of the Washington Convention Center.

Julian Adams, Ph.D., Chief Scientific Officer, Infinity Pharmaceuticals, Cambridge, Mass., will be the recipient of the 25th AACR-Bruce F. Cain Memorial Award. He is being honored for the synthesis of the first selective proteasome inhibitor, bortezomib (VELCADE), for recognizing the potential of a proteasome inhibitor as a novel cancer therapeutic, and for appreciating the relationship between the proteasome, NF-kB and multiple myeloma. This award, established in 1982 by the AACR and Warner Lambert Company (now Pfizer), recognizes an individual or research team for outstanding preclinical research in the fields of medicinal chemistry, biochemistry or tumor biology as related to drug discovery that has implications for the improved care of cancer patients. The prize was established to honor Dr. Bruce F. Cain, whose scientific interests involved the design, synthesis, and biological evaluation of potential anti-tumor drugs. Adams will present his lecture, “The Proteasome and Cancer: The Discovery and Development of VELCADE,” at 9:00 a.m., April 5, in Ballroom A-B of the Washington Convention Center.

Nicholas Edward Day, Ph.D., Professor of Epidemiology, University of Cambridge, UK, will be honored with the 15th AACR-American Cancer Society Award for Research Excellence in Cancer Epidemiology and Prevention. With this award, Day will be recognized for developing and widely applying many of the statistical methods that support modern cancer epidemiology. The award is intended to distinguish outstanding achievements in the fields of epidemiology, biomarkers, and prevention. Day will present his lecture on “Cancer Prevention: Past Perspectives and Future Directions,” at 5:30 p.m. on Tuesday, April 4, in Hall D of the Washington Convention Center.

Merrill J. Egorin., M.D., Professor of Medicine and Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh, Pa., will be honored in recognition of his outstanding achievements in clinical and preclinical cancer pharmacology. Dr. Egorin will be the recipient of the 11th AACR-Joseph H. Burchenal Clinical Research Award, which recognizes outstanding achievements in clinical cancer research. The award’s namesake was an honorary member and past president of AACR, as well as a major figure in clinical cancer research. Dr. Egorin’s lecture, “Keep on Trucking: Antineoplastic Clinical Pharmacology—Where We Have Been, and Where We Need to Go,” is to be presented at 8:00 a.m., Wednesday, April 5, in Ballroom A-B of the Washington Convention Center.

Ivan Dikic, M.D., Ph.D., a professor in the Institute for Biochemistry II, Goethe University Medical School in Frankfurt, Germany, is the recipient of the 26th AACR Award for Outstanding Achievement in Cancer Research as an accomplished young investigator in the field who is no more than 40 years old at the time the award is conferred. Dr. Dikic will be honored for his groundbreaking contributions to the field of receptor tyrosine kinase (RTK) signaling and regulation during his short and yet remarkably productive career as an independent investigator. Dr. Dikic’s lecture, “Ubiquitination in Cellular Signaling and Cancer Pathogenesis,” will be given at 1:00 p.m. on Tuesday, April 4, in Hall D of the Washington Convention Center.

Nancy Hopkins, Ph.D., the Amgen, Inc. Professor of Biology at the Massachusetts Institute of Technology in Cambridge, will be honored with the 9th AACR-Women in Cancer Research-Charlotte Friend Memorial Lectureship. Hopkins was chosen for her unprecedented success in cloning vertebrate developmental genes by exploiting zebra fish as an ideal model organism, and also for her revolutionary work on gender equity issues in science. Named for the renowned virologist and discoverer of the Friend virus, Dr. Charlotte Friend, 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. Hopkins will present her lecture, “Genes for Development and Disease in Zebrafish,” at 6:15 p.m. on Saturday, April 1, in Ballroom A of the Washington Convention Center.

Editors Note: Additional award information is available by clicking 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 60 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.

Contact:

Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

The American Association for Cancer Research Provides Support for Promising Cancer Scientists

registration@aacr.org () — Wed, 22 Mar 2006 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. This year, the AACR has selected 15 investigators to receive these career development awards and research grants, which total commitments to $915,000. 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’s 97th Annual Meeting, to be held April 1-5, 2006, in Washington, D.C.

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: Scott M. Hammond, Ph.D., University of North Carolina, Chapel Hill, N.C.
Project: The Role of microRNAs in tumorigenesis

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. Each award provides a two-year grant of $50,000 per year.

Award in Translational or Prevention Lung Cancer Research, given in memory of Lloyd Meeds
Recipient: Herta Huey-An Chao, M.D., Ph.D., Yale University, New Haven, Conn.
Project: The detection of pharmacodynamic changes in circulating tumor cells in response to chemotherapy using a novel robotic epifluorescent microscopy platform

AACR-Genentech BioOncology Career Development Award for Cancer Research on the HER Family Pathway
Recipient: Jayanta Debnath, M.D., University of California, San Francisco, Calif.
Project: The role and regulation of autophagy downstream of HER family pathways

AACR-PanCAN Michael Landon Career Development Award in Pancreatic Cancer Research
Recipient: Daoyan Wei, Ph.D., The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Project: The role of KLF4a in pancreatic cancer

AACR-PanCANCareer Development Award in Pancreatic Cancer Research
Recipient: David Z. Chang, M.D., Ph.D. The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Project: Identification and verification of novel tumor antigens for cancer vaccine development in pancreatic carcinoma

AACR-Pennsylvania Department of Health Career Development Award in Basic Cancer Research (one-year grant)
Recipient: Edna Cukierman, Ph.D., Fox Chase Cancer Center, Philadelphia, Pa.
Project: In vivo-like 3D system to assess stroma permissiveness in tumor cell invasion

RESEARCH FELLOWSHIPS
The AACR Research Fellowships were established in 1996 in response to the growing need for additional funds to train early career scientists by providing grants of $35,000-$40,000 per year for one, two, or three years.

AACR-Genentech BioOncology Fellowship for Cancer Research on Angiogenesis
Recipient: Marco Seandel, M.D., Ph.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Project: Regulation of bone marrow endothelium and endothelial progenitors by androgens in prostate cancer

AACR-Amgen, Inc. Fellowship in Clinical/Translational Cancer Research
Recipient: Andrew J. Armstrong, M.D., Johns Hopkins University, Baltimore, Md.
Project: A pharmacodynamic study of pre-prostatectomy rapamycin in men with advanced localized prostate cancer
Recipient: Rupal Satish Bhatt, Ph.D., M.D., Beth Israel Deaconess Medical Center, Boston, Mass.
Project: ANGPTL4 as a potentially novel biomarker and/or therapeutic angiogenic target for renal cell cancer

AACR-MedImmune Fellowship for Research on Biologics-Based Therapies for Cancer
Recipient: Robert R. Jenq, M.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Project: Augmentation of immune responses to melanoma DNA vaccines after allogeneic bone marrow transplantation using interleukin-7 and keratinocyte growth factor

AACR Fellowship in Clinical Cancer Research
Recipient: Catherine S. Magid Diefenbach, M.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Project: YKL-40: A novel serum marker for the detection of epithelial ovarian cancer and a target for tumor directed therapy

AACR-AstraZeneca-Cancer Research and Prevention Foundation Fellowship in Translational Lung Cancer Research
Recipient: Anil Potti, M.D., Duke University Medical Center, Durham, N.C.
Project: Gene expression signatures of oncogenic pathway deregulation provide a novel approach to selection of molecular targets in recurrent non-small cell lung carcinoma

AACR-Anna D. Barker Fellowship in Basic Cancer Research
Recipient: Shih-Peng Chan, Ph.D., Yale University, New Haven, Conn.
Project: Potential oncogenes encoding microRNA binding proteins

AACR-Cancer Research and Prevention Foundation Melanoma Research Fellowship, given in memory of H. Theodore Shore
Recipient: Juan Chen, M.D., University of Miami School of Medicine, Miami, Fla.
Project: Two novel laminins in the angiogenesis and progression of melanomas

FELLOWS GRANT
The Fellows Grants provides a one-year grant of $25,000 to a fellow to pursue an independent line of investigation within the context of his/her current fellowship placement.

AACR-Pennsylvania Department of Health Fellows Grant
Recipient: Sibele I. Meireles, Ph.D., Fox Chase Cancer Center, Philadelphia, Pa.
Project: Contribution of estrogen synthesis and detoxification enzyme expression to tobacco smoke-induced lung 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 60 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.

Contact:

Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

Pezcoller Foundation-AACR International Award for Cancer Research Honors Discoveries in Cellular and Molecular Immunology

registration@aacr.org () — Mon, 20 Mar 2006 12:00:00 GMT

Tadatsugu Taniguchi was first to identify and characterize interferon and interleukin genes, and to discover the IRF transcription factor family

PHILADELPHIA – Tadatsugu Taniguchi, Ph.D., professor and chairman of the Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Japan, is the recipient of the 10th annual Pezcoller Foundation-American Association for Cancer Research International Award for Cancer Research, for his pioneering work in elucidating the complex genetic structure of the immune system, which has had a profound impact on cancer research and molecular immunology.

The annual award, established in 1997, recognizes an individual who has made a major scientific discovery in basic or translational cancer research.

Taniguchi will give an award lecture at the 97th AACR Annual Meeting in Washington, D.C., April 1-5, 2006. His talk, titled “Cytokines and IRFs in the Regulation of Oncogenesis and Immunity,” is scheduled for noon, on Sunday, April 2, in Hall D of the Washington Convention Center. In honor of Taniguchi, the Pezcoller Foundation will hold an award ceremony later in the spring, at its location in Trento, Italy. Taniguchi will receive a cash prize of €75,000 and a medallion.

“Dr. Taniguchi is truly a pioneer in cancer research at the molecular level,” said AACR chief executive officer Margaret Foti, Ph.D., M.D. (h.c.). “By unraveling the complex mechanisms by which the human body defends itself against disease, he broadened exponentially our understanding of cancer and our capacity to treat cancer successfully.

“Among his many contributions to cancer research,” Foti added, “Dr. Taniguchi discovered interferon regulatory factors, a family of transcription factors that are involved in programmed cell death and tumor suppression, and have important implications for cancer therapy.”

“It is a great honor to receive this recognition from my peers and colleagues,” Taniguchi said. “All of us who do research and teach are enriched by our collaborations. I have been particularly privileged to work in the United States and Europe, and to be part of a global scientific community. I hope we will continue to gain new insights into immune defense mechanisms, and I look forward to the day when our global and interdisciplinary efforts make the deadliest and most debilitating diseases a distant memory.”

Taniguchi began the study of cytokines—proteins that regulate the intensity and duration of immune response and mediate cell communication—at The Cancer Institute of Japanese Foundation of Cancer Research, after his return to Tokyo from the University of Zurich, Switzerland, where he obtained his Ph.D. degree under the tutelage of Charles Weissmann. There, in the late 1970s, he identified the human interferon-beta gene, making it possible to elucidate for the first time the complete primary structure of a cytokine: At the same time, the structure of interferon-alpha was elucidated by his mentor in Zurich, and together they went on to demonstrate that interferon-alpha and interferon-beta constitute a gene family.

“In retrospect, this turned out to be the first of the numerous cytokine gene families to be identified, and I am so grateful to Charles, whom I consider as my father in science, for his continuous support,” said Taniguchi. “We also identified and characterized a human interleukin gene, the IL-2 gene.”

Interferons and interleukins both are produced naturally in the body and can improve the body’s natural response to infection and disease. Interferons interfere with the division of cancer cells and can slow tumor growth; interleukin-2, discovered by Robert Gallo and colleagues, stimulates the growth of disease fighting white blood cells in the immune system.

The identification of these cytokine genes have made it possible to create interferons and IL-2 in the laboratory, making recombinant cytokines available for use in clinical applications involving cancer, hepatitis and multiple sclerosis, as well as for studies of the mechanisms of molecular signaling. Taniguchi then discovered a novel family of transcription factors, the IRF family, and elucidated the critical functions of these factors in immunity and oncogenesis.

Prior to joining the medical faculty at the University of Tokyo in 1995, Taniguchi was a professor at the Institute for Molecular and Cellular Biology at Osaka University, and held positions of escalating importance with the Cancer Institute of the Japanese Foundation for Cancer Research in Tokyo. He was a visiting associate professor and now an adjunct professor at New York University Medical Center. Early in his research career, he was also trained by Massimo Libonati in the Laboratory of Biological Chemistry at the University of Naples, Italy.

Taniguchi has published more than 200 papers and is the recipient of many major honors, including the Hammer Prize, Behring-Kitasato Prize, the Robert Koch Prize and Lifetime Membership Award of the International Cytokine Society. He is a Foreign Associate Member in the U.S. National Academy of Sciences. An active member of the AACR since 1991, Taniguchi serves as co-chairperson of the AACR International Affairs Committee and is Associate Editor of Cancer Research.

A series of awards are given annually by the AACR—the world’s oldest and largest professional society representing cancer scientists from the United States and more than 60 other countries—to recognize world-class accomplishments in basic and translational research, clinical care, therapeutics and prevention.

Editors Note: A photograph of Tadatsugu Taniguchi can be obtained here.

# # # #

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 generous gift in support of the formation of the Foundation, stimulated others to make significant advances in cancer research. The Foundation sponsors a series of symposia and publishes a journal. In the past, the Pezcoller Foundation gave a biennial award for contributions to cancer and cancer-related biomedical science in collaboration with the European School of Oncology. The Pezcoller Foundation-AACR International Award, which has been given annually since 1997, builds upon that tradition.

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 60 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.

Contact:

Elizabeth J. Tait
215-440-9300 ext. 144
tait@aacr.org

AACR Expands Cancer Research Knowledge with Scholarships for Minority and Women Scientists

registration@aacr.org () — Fri, 17 Mar 2006 12:00:00 GMT

118 Receive Scholar Awards to Participate in American Association for Cancer Research Annual Meeting in Washington, DC, April 1-5, 2006

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. The AACR Annual Meeting draws nearly 16,000 clinical oncologists, basic scientists, epidemiologists and translational researchers from around the world to 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.”

77 early-career scientists received AACR Minority Scholar Awards in Cancer Research to participate in the 2006 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 69 awardees will 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.

The Minority Scholar Awards are supported generously by grants from the Comprehensive Minority Biomedical Branch of the National Cancer Institute and the Susan G. Komen Breast Cancer Foundation.

The AACR Minority-Serving Institution Faculty Scholar Awards in Cancer Research aims to increase the scientific knowledge base of faculty members at Minority-Serving Institutions, encourage their research, and help them to inspire their students. Formally 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 and the Susan G. Komen Breast Cancer Foundation.
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 31 AACR-MSI Faculty Scholars chosen this year will receive financial support toward expenses associated with attending the AACR Annual Meeting or Special Conferences.

A committee of the AACR Minorities in Cancer Research Council administers both of these award programs.

The AACR-Women in Cancer Research Brigid G. Leventhal Scholar Awards in Cancer Research 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 2006. 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 can be found 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 60 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.

Contact:

Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

Tomorrow’s Cancer Researchers to Attend the 97th Annual Meeting

registration@aacr.org () — Fri, 17 Mar 2006 12:00:00 GMT

PHILADELPHIA – To provide some enlightenment about cancer research as a career option, the American Association for Cancer Research will host a series of special programs for young scientists at the 97th Annual Meeting: the AACR-Thomas J. Bardos Science Education Awards for Undergraduate Students, the Undergraduate Student Caucus, and the AACR Special Program for High School Students. This year’s Annual Meeting will take place April 1-5 at the Washington Convention Center, Washington, D.C. The programs are organized by the AACR Science Education Committee and are designed to give students the opportunity to network with each other and leaders in the field of cancer research.

Twenty-one undergraduate students will come to Washington, D.C. as recipients of the AACR-Thomas J. Bardos Science Education Awards. The students include 10 winners from 2006-2007, along with 11 winners from 2005-2006 who also attended last year’s Annual Meeting in Anaheim. To qualify for the award, candidates must be full-time, third-year undergraduates majoring in science.

Dr. 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 and still holds emeritus status. Thanks to Dr. Bardos’ support and dedication, recipients of the award receive a stipend to attend two consecutive Annual Meetings. His contributions are matched by the AACR.

In addition, all undergraduate student Annual Meeting registrants are invited to participate in the Undergraduate Student Caucus taking place from noon to 4:00 p.m., on Sunday, April 2, 2006, in the Grand Ballroom North in the Renaissance Washington Hotel. This year’s keynote speaker will be Donald S. Coffey, Ph.D., from the Johns Hopkins University School of Medicine in Baltimore, Md. The caucus will provide a forum for undergraduate students to discuss with early career scientists, the issues important to scientific research and the next stages in their career development.

Bardos Award winners will be made Student Members of the AACR. A list of their names and affiliations, in alphabetical order by state is available here (Adobe Acrobat Reader required).

Along with undergraduate programs, about 300 students from the Washington D.C. area will take part in the AACR Special Program for High School Students. This program features lectures from several distinguished scientists, a Student Presentation and Networking Reception, and a Mentor-escorted tour of the exhibit and poster area. It will take place at 9:30 a.m. on Monday, April 3, 2006, in Room 201 of the Washington Convention Center.

Editors Note: Members of the media are welcome to attend the Special Program for High School Students.

# # # #

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 60 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.

Contact:

Angela DeCicco
215-440-9300 ext. 104
decicco@aacr.org

Leading Breast Cancer Researcher Awarded New Lectureship

registration@aacr.org () — Fri, 17 Mar 2006 12:00:00 GMT

Olopade is Recipient of the Inaugural AACR-Minorities in Cancer Research-Jane Cooke Wright Lectureship

PHILADELPHIA -- Olufunmilayo I. Olopade, M.D., director of the Center for Clinical Cancer Genetics at the University of Chicago Medical Center, is the inaugural recipient of the AACR-Minorities in Cancer Research-Jane Cooke Wright Lectureship. The award is given to 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.

The award, sponsored by AACR-Minorities in Cancer Research, is named in honor of Jane Cooke Wright, M.D., a pioneer in clinical cancer chemotherapy and an exceptional scientist who is African-American and who has made important contributions to research in this field.

Dr. Olopade is being recognized for her pre-eminent research in breast cancer. An international leader in the field, her application of a multidisciplinary laboratory and clinical approach in cancer genetics has led to strategies for prevention and/or early detection in patients at high risk for breast cancer and to the identification of novel BRCA-1 mutations in African-American families with a history of familial breast cancer.

Her discovery of a putative tumor suppressor gene involved in several other solid tumors eventually led to the identification of p16INK4. Dr. Olopade’s perspective on the importance of translating research findings to clinical application is consistent with the philosophy of Dr. Wright.

As a physician-scientist, she has mentored numerous fellows and served as role model to many young scientists participating in cancer research. Her enthusiasm and accomplishments have inspired many junior faculty and fellows pursuing careers in academic medicine.

Dr. Olopade received her medical degree with distinction from the University of Ibadan in Nigeria. She came to the United States as a resident in internal medicine at Cook County Hospital in Chicago where she was named Chief Medical Resident. Upon completion of her Hematology/Oncology Fellowship training at the University of Chicago, she was appointed to the faculty in 1991 and rose to the rank of full professor in 2002. Dr. Olopade is the recipient of numerous honors and awards including the Doris Duke Distinguished Clinical Scientist Award and a MacArthur Fellowship “genius” grant.

Dr. Olopade will give a lecture during the AACR 97th Annual Meeting in Washington, D.C. The lecture will take place 8:00 a.m., Tuesday, April 4, 2006 in Ballroom A of the Washington Convention Center. In addition to the lectureship, Dr. Olopade will also receive an honorarium and a commemorative plaque.

Editors Note: To download a high resolution photograph of Dr. Olopade and for further information on this lectureship, click 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 60 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.

Contact:

Yarissa Ortiz
215-440-9300 ext. 101
ortiz@aacr.org

AACR Supports the Nomination of Andrew von Eschenbach as the Commissioner of the U.S. FDA

registration@aacr.org () — Wed, 15 Mar 2006 12:00:00 GMT

PHILADELPHIA – The American Association for Cancer Research, the world’s oldest and largest organization dedicated to cancer research, enthusiastically supports the nomination of Andrew von Eschenbach as new commissioner of the U.S. Food and Drug Administration.

“Dr. von Eschenbach brings enormous medical and administrative expertise and experience to this post,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “This background will be vitally important in his new challenging role of FDA commissioner.”

In the cancer community, Dr. von Eschenbach, 64, is a well-recognized urologic surgeon who formerly directed the Genitourinary Cancer Center and the Prostate Cancer Research Program at The University of Texas M. D. Anderson Cancer Center. Dr. von Eschenbach spent a quarter of a century there, moving from faculty member to department chair to executive vice president and chief academic officer.

Subsequently, Dr. von Eschenbach was named Director of the National Cancer Institute, the 12th person to assume this responsibility in the NCI’s 67-year old history. During his tenure, he worked to strengthen collaborations between the NCI and the FDA, and to bring laboratory breakthroughs to the clinic as quickly as possible, maximizing patient benefits and minimizing risks. As part of this collaboration, the NCI and FDA – through a joint agency task force – agreed to share knowledge and resources to facilitate the development of new cancer drugs and speed their delivery to patients.

“Dr. von Eschenbach also has a special appreciation for translational cancer research, the process that bridges basic research with clinical research, with the goal of bringing new discoveries to the cancer patient,” said Peter Jones, Ph.D., D.Sc., AACR president and director of the University of Southern California/Norris Comprehensive Cancer Center and Distinguished Professor of Urology and Biochemistry & Molecular Biology at the Keck School of Medicine at USC.

“His knowledge of the health delivery system at all levels -- as a medical researcher, cancer physician and as a leader of a major government health agency – lend support to his qualifications as FDA commissioner,” Jones added.

Among his other professional activities, Dr. von Eschenbach was president-elect of the American Cancer Society, and also served as a speaker in public outreach programs organized by the AACR. He is a three-time survivor of cancer, giving him an added perspective of a patient who faced a life-threatening disease.

“Dr. von Eschenbach not only brings a wealth of scientific knowledge to the FDA post, he also brings the personal experiences of a cancer patient and survivor,” said Foti.

# # # #

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 60 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.

Contact:

Warren R. Froelich
215-440-9300 ext. 198
froelich@aacr.org

Cells in Mucus from Lungs of High-Risk Patients Can Predict Tumor Development

registration@aacr.org () — Wed, 15 Mar 2006 12:00:00 GMT

PHILADELPHIA -- In a group of high-risk patients, a test that examined DNA from cells expelled in sputum for evidence of “silenced” genes correctly identified the majority of patients who were later diagnosed with lung cancer, say researchers in a study published in the March 15 issue of Cancer Research.

As such, the sputum test potentially represents a unique, non-invasive, and cost-effective screening method that could lead to earlier treatment of lung cancer. “Short of repeatedly X-raying a person’s lungs to look for emerging tumors, there is no way now to screen people at high risk for lung cancer, much less predict who will be diagnosed with the cancer at a later date,” said the study’s senior author, Steven Belinsky, Ph.D., director of the Lung Cancer Program at the Lovelace Respiratory Research Institute in Albuquerque, N.M.

“When perfected and validated, this kind of test holds great promise for identifying people with lung cancer early enough to successfully treat them,” he said. The test was able to predict which patients would develop lung cancer up to 18 months later. Catching lung tumors within that short timeframe can change a patient’s outcome, Belinsky said, because these cells often proliferate rapidly after a long slow-growth period. “Because most people are diagnosed when their cancer is advanced, they may not benefit from surgery, chemotherapy or radiation, which is why median survival from diagnosis is only 13 months,” he said. “But lung tumors that can be surgically removed are associated with a five year survival rate of more than 60 percent.”

The researchers are now working to perfect the test because it is not yet accurate enough for the clinic. It identified 65 percent of individuals who later developed symptoms of lung cancer, but also tagged 35 percent of cancer-free control participants. “Our hope is that our continuing research will identify additional genes that will make a sputum test like this highly predictive,” Belinsky said.

The test is also unique because it examines cells sloughed off in sputum for evidence that genes have been “turned off,” in contrast to the more traditional “biomarker” assays that look for increased gene activity.

Belinsky and his research team developed the test by identifying genes known to be “hypermethylated” in lung cancer -- that is, decorated with molecules known as methyl groups that function to turn a gene off. Stephen Baylin, M.D., and James Herman, M.D., from Johns Hopkins Kimmel Cancer Center, Baltimore, Md. -- who are co-authors of this study -- are recognized leaders in this area of research. Addition of these methyl groups to the DNA base cytosine modifies histone proteins, which act like spools around which DNA winds itself.

Histones play a role in gene regulation, and when altered, prevent genes from being transcribed into proteins, according to Belinsky. These modifications to a gene’s promoter region offer scientists a biomarker to determine which genes have been hypermethylated, and a panel of such markers can form an assay, he said. This assay uses stretches of artificial DNA that can attach only to specific methylated genes.

In this study, Belinsky worked with researchers at University of Colorado Health Sciences Center, Denver, Colo., to develop a blinded and nested case-control study within their Sputum Screening Cohort Study, which has been ongoing since 1993. The Colorado researchers asked whether mucus that coats all parts of the lung can contain genetic evidence of cancer cells when expelled in sputum. Their study enrolled patients who all had a history of smoking and chronic obstructive pulmonary disease. Belinsky and the researchers examined sputum from 98 people who developed cancer, and compared these samples to 92 participants who did not.

They looked at silencing of 14 genes known to be inactivated at different stages of lung cancer development, and found that six of these genes served to predict who would develop lung cancer. These genes are P16, PAX5-beta, MGMT, DAPK, GATA5, RASSF1A. Then, they found that participants who had three or more of these methylated, silenced genes in sputum, collected within 18 months of diagnosis, had a 6.5-fold increase risk for lung cancer.

The test didn’t work well if the sputum was collected more than 18 months before lung cancer was diagnosed, Belinsky said. “The prevalence for methylation of gene promoters increased as the time to lung cancer diagnosis decreased,” he said.

A person who tests positive for the test would receive a follow-up diagnostic bronchoscopy or X-ray to determine if tumors exist, Belinsky said. If tumors are not evident, patients could be retested in several months. He added that the test might also be used in the future to help guide drug therapy. A new class of therapeutic drugs is being developed that are designed to reduce methylation in genes and restore their function, Belinsky explained. “When a number of these agents come on the market, then an improved sputum test could be used to match these agents to genes individual patients have lost,” he said. “We can then use this kind of test diagnostically.”

In addition to Belinsky, Herman, and Baylin, study co-authors include Kieu Liechty and Frederick Gentry at the Lovelace Respiratory Research Institute; Holly Wolf, Justin Rogers, Kieu Vu, Jerry Haney, Tim Kennedy, Fred Hirsch, York Miller, Wilbur Franklin, Paul Bunn and Tim Byers at the University of Colorado Health Sciences Center; and James Herman, Johns Hopkins Kimmel 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. Our members include more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 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, and funding meritorious research projects. The AACR Annual Meeting attracts some 16,000 participants who share the latest discoveries and developments. Special Conferences throughout the year present novel information across a wide variety of cancer research and patient care topics. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention, as well as CR, a magazine about people and progress in cancer.

Contact:

Russell Vanderboom, Ph.D.
215-440-9300 ext. 120
vanderboom@aacr.org

Pepper Component Hot Enough to Trigger Suicide in Prostate Cancer Cells

registration@aacr.org () — Wed, 15 Mar 2006 12:00:00 GMT

PHILADELPHIA – Capsaicin, the stuff that turns up the heat in jalapeños, not only causes the tongue to burn, it also drives prostate cancer cells to kill themselves, according to studies published in the March 15 issue of Cancer Research.

According to a team of researchers from the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, in collaboration with colleagues from UCLA, the pepper component caused human prostate cancer cells to undergo programmed cell death or apoptosis.

Capsaicin induced approximately 80 percent of prostate cancer cells growing in mice to follow the molecular pathways leading to apoptosis. Prostate cancer tumors treated with capsaicin were about one-fifth the size of tumors in non-treated mice.

“Capsaicin had a profound anti-proliferative effect on human prostate cancer cells in culture,” said Sören Lehmann, M.D., Ph.D., visiting scientist at the Cedars-Sinai Medical Center and the UCLA School of Medicine. “It also dramatically slowed the development of prostate tumors formed by those human cell lines grown in mouse models.”

Lehmann estimated that the dose of pepper extract fed orally to the mice was equivalent to giving 400 milligrams of capsaicin three times a week to a 200 pound man, roughly equivalent to between three and eight fresh habañera peppers – depending on the pepper’s capsaicin content. Habañeras are the highest rated pepper for capsaicin content according to the Scoville heat index. Habañero peppers, which are native to the Yucatan, typically contain up to 300,000 Scoville units. The more popular Jalapeño variety from Oaxaca, Mexico, and the southwest United States, contains 2,500 to 5,000 Scoville units.

As described in their study, the scientists observed that capsaicin inhibited the activity of NF-kappa Beta, a molecular mechanism that participates in the pathways leading to apoptosis in many cell types.

Apoptosis is a normal cellular event in many tissues that maintains a balance between newer replacement cells and aged or worn cells. In contrast, cancer cells seek to be immortal and often dodge apoptosis by mutating or deregulating the genes that participate in programmed cell death.

“When we noticed that capsaicin affected NF-kappa Beta, that was an indication that we might expect some of the apoptotic proteins to be affected,” said the study’s senior author, Phillip Koeffler, M.D., director of Hematology and Oncology, Cedars-Sinai Medical Center, and professor at UCLA.

The pepper extract also curbed the growth of prostate cancer cells through regulation of androgen receptors, the steroid activated proteins that control expression of specific growth relating genes.

In prostate cancer cells whose growth is dependent on testosterone, the predominant male sex steroid, capsaicin reduced cell proliferation in a dose-dependent manner. Increased concentrations of capsaicin caused more prostate cancer cells to freeze in a non-proliferative state, called G0/G1.

Prostate cancer cells that are androgen independent reacted to capsaicin in a similar manner. Capsaicin reduced the amount of androgen receptor that the tumor cells produced, but did not interfere with normal movement of androgen receptor into the nucleus of the cancer cells where the steroid receptor acts to regulate androgen target genes such as prostate specific antigen (PSA). Capsaicin also interfered with the action of androgen receptors even in cells that were modified to produce excess numbers of androgen receptors.

The hot pepper component also reduced cancer cell production of PSA, a protein that often is produced in high quantities by prostate tumors and can signal the presence of prostate cancer in men. PSA content in the blood of men is used as a diagnostic prostate cancer screening measure. PSA is regulated by androgens, and capsaicin limited androgen-induced increases of PSA in the cancer cell lines.

More men in the United States develop prostate cancer than any other type of malignancy. Every year, more than 232,000 new cases of prostate cancer are diagnosed in the U.S., and more than 680,000 develop the disease worldwide. Approximately 30,000 men die from prostate cancer in the U.S. each year, which is about 13 percent of all new cases. Worldwide, there are 221,000 deaths – approximately 31 per cent – among men with prostate cancer.

Lehman conducted the studies in Koeffler’s laboratory in collaboration with UCLA cancer researchers Akio Mori, James O’Kelly, Takishi Kumagai, Julian Desmond, Milena Pervan, and William McBride. Mosahiro Kizaki, a former post-doctoral fellow in Koeffler’s laboratory who initiated the capsaicin studies, is currently at the Keio University School of Medicine, Tokyo, Japan.

# # # #

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. Our members include more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 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, and funding meritorious research projects. The AACR Annual Meeting attracts some 16,000 participants who share the latest discoveries and developments. Special Conferences throughout the year present novel information across a wide variety of cancer research and patient care topics. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention, as well as CR, a magazine about people and progress in cancer.

Contact:

Russell Vanderboom, Ph.D.
215-440-9300 ext. 120
vanderboom@aacr.org

OBITUARY: JOSEPH H. BURCHENAL (1912-2006)

registration@aacr.org () — Fri, 10 Mar 2006 12:00:00 GMT

Past AACR President and Cancer Chemotherapy Pioneer

Joseph H. Burchenal, one of the true pioneers of cancer chemotherapy and past president of AACR, died Wednesday, March 8, 2006. He was 93.

“The work of Dr. Burchenal and his colleagues had an immeasurable impact, saving countless lives of patients with cancer,” said Margaret Foti, Ph.D., M.D. (h.c.), AACR chief executive officer. “His legacy is one of compassionate patient care, constant scientific curiosity, mentorship to future scientists, and meticulous attention to detail in the design, execution and reporting of the results of clinical trials.”

Dr. Burchenal’s medical career began when the word “chemotherapy” was used principally to identify methods for treating malaria, syphilis and bacterial infections. Indeed, during World War II and immediately thereafter, he served as Chief of Infectious Disease at the Harvard Fifth General Hospital in Northern Ireland, England and France, and as Chief of Tropical Medicine at the Walter Reed Hospital.

Upon discharge from the military, Dr. Burchenal joined the staff of the Memorial Hospital and Sloan Kettering Institute, where he remained until his retirement. Throughout the 1950s, his work and the work of other pioneering clinicians at Sloan Kettering led to the introduction of the earliest classes of anti-cancer agents – such as nitrogen mustards, oral alkylating agents, folate antagonists – and to clinical trials using these new agents in the first combination regimens.

In the 1960s, his collaborations with Dennis Burkitt, Herbert Oettgen and Peter Clifford yielded the first meaningful treatments for patients in Africa suffering from head and neck cancers, subsequently called “Burkitt’s tumor.” Dr. Burchenal authored more than 700 peer-reviewed publications.

His career also was marked by a wealth of important advisory roles, as an officer and committee member for many professional organizations. Aside from serving as President of AACR (1965-66), he was a member of the Board of Directors (1963-68), and was elected an Honorary Member of the Association in 1987.

In 1996, the AACR-Joseph H. Burchenal Clinical Research Award was established in his honor as a major figure in clinical cancer research. This award is presented annually to a researcher who has made significant contributions to clinical care in the field of cancer.

In addition to his AACR service, Dr. Burchenal was an advisor to U.S. Senate committees, the NCI, and many other professional organizations. He received a host of awards, including the Alfred P. Sloan Award (1963); Prix Leopold Griffuel (1970); the Albert Lasker Award in Clinical Cancer Chemotherapy (1972); the David A. Karnofsky Memorial Award of the American Society of Clinical Oncology (1974); the James Ewing Award (1975); the American Cancer Society Annual Award (1982); the Return of the Child Award of the Leukemia Society of America (1986); and the Distinguished Scientific Award of ASCO (1994).

Leading Cancer Research Organization Elects New Leadership

registration@aacr.org () — Thu, 09 Mar 2006 12:00:00 GMT

American Association for Cancer Research chooses officers, directors and nominating committee members for 2006 and beyond

PHILADELPHIA—William N. Hait, M.D., Ph.D., director of The Cancer Institute of New Jersey, New Brunswick, N.J., will become president-elect of the American Association for Cancer Research effective April 3, 2006, at the 97th AACR Annual Meeting in Washington, D.C.

He succeeds Geoffrey M. Wahl, of The Salk Institute for Biological Sciences in La Jolla, Calif., who was chosen president-elect at the 2005 meeting and who will accede to the presidency this year.

Peter A. Jones, Ph.D., D.Sc., director of the University of Southern California./Norris Comprehensive Cancer Center in Los Angeles, who has served as AACR president for the 2005-2006 term, will fulfill the role of past president.

The president, president-elect and past president serve terms of one year, comprising the period between annual meetings, which typically are held in April.

William N. Hait, M.D., Ph.D., has been 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 since 1993. His principal research interests include breast cancer, drug development, calcium-mediated signal transduction, multidrug resistance, translational research and clinical pharmacology. Specifically, his laboratory focuses on the determinants of sensitivity to anticancer treatments and signal transduction systems uniquely altered in malignant cells. The research spans molecular and cellular biology to tissue culture and animal models, ultimately arriving in the clinic.

“The AACR stands as a beacon for those who understand and therefore value the importance of excellence in research to the ultimate conquest of cancer,” Hait said. “The AACR offers cancer researchers their most natural professional home because of its diverse scientific membership that spans laboratory, translational, clinical, and population research; its vibrant activities for advocates and survivors; its multiple mechanisms for exchange of information including regional, national and international meetings; and its robust publishing division.”

Hait was named editor-in-chief of the AACR journal Clinical Cancer Research in 2005, and is associate editor of the AACR’s flagship publication, Cancer Research. His further service to the AACR includes chairing the Clinical Cancer Research Committee and membership on committees that deal with clinical research, pharmacology and experimental therapeutics. Further, he is an expert in science policy and regulatory affairs pertaining to oncologic drugs, and was the AACR representative to the U.S. Food and Drug Administration.

A native of Newark, N.J., Hait received his undergraduate degree from the University of Pennsylvania and earned his M.D. and Ph.D. from the Medical College of Pennsylvania in 1978. He joined the faculty of the Yale University School of Medicine in 1984, after serving his internship there, and was promoted to associate professor of medicine and pharmacology. Hait served as associate director of the Yale University Comprehensive Cancer Center, director of the Breast Cancer Unit and co-director of the Lung Cancer Unit at the Yale University School of Medicine. He was appointed chief of medical oncology at the Yale University School of Medicine in 1988. Hait briefly was acting chief of medical oncology at the West Haven Veterans Administration Hospital in West Haven, Conn., before joining UMDNJ and CINJ.

Geoffrey M. Wahl, Ph.D., is the new AACR president. He 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. His research interests include molecular biology and the genetics of cancer; genetic instability during cancer initiation and progression; cellular responses to chemotherapeutic agents; oncogene signaling and other stresses related to cancer development or treatment; initiation of DNA replication in normal and malignant cells; and development of targeted therapeutics.

Wahl and his colleagues have investigated mechanisms of genetic instability in cancer cells, which led to their demonstration that integrity of the p53 tumor suppressor pathway is essential for maintaining genome stability. Their current research uses the p53 pathway as a model to understand the mechanisms by which normal and cancer cells sense and respond to the diverse stresses that contribute to cancer development. Using animal and in vitro two-dimensional and three-dimensional models, they investigate how p53 structure – and the regulatory proteins with which it interacts – enables different gene expression patterns to be elicited depending on the stress and tissue in which the system is activated. Wahl and his group are integrating this information to develop molecularly targeted therapies to activate the p53 pathway to induce cell death in the significant fraction of cancers that retain wild type p53 genes.

Wahl earned his doctorate in biological chemistry at Harvard University, and did post-doctoral research at Stanford University. He served three years on the Executive Committee, Integration Panel, Department of Defense Cancer Research Program. Awards include that for Outstanding Contributions to Science Education, given by the San Diego Science Educators’ Association and the “Citation Classic” Designation for One of the Most Highly Cited Scientific Papers, 1961-1982.

Previously, he 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 the journals Molecular Cancer Research and Cell Growth and Differentiation; as well as holding numerous other, special conference chairs and committee posts.

Peter A. Jones, Ph.D., D.Sc., AACR’s outgoing president, is director of the University of Southern California/Norris Comprehensive Cancer Center; director of the Urological Research Laboratories; and distinguished professor of biochemistry and molecular biology and urology at the Keck School of Medicine of USC. Jones also holds the H. Leslie and Elaine S. Hoffman Cancer Research Chair at the University of Southern California.

He studies how cancer-related genes become heritably silenced during carcinogenesis, resulting in functional inactivation. The primary focus of his research is on DNA cytosine methylation and how this process interacts with chromatin structure to ensure heritable silencing. He also is interested in translating basic scientific discoveries into clinical treatments, specifically for human bladder cancer. He and his colleagues are working on drugs that can reverse silencing and turn genes back on again, and designing strategies where this kind of epigenetic therapy can be applied to the treatment of human cancers.

Born, raised and educated in the former Rhodesia (now Zimbabwe), Jones received his doctor of philosophy degree from the University of London in 1973. He joined the University of Southern California in 1977, attaining the rank of professor in 1985, and becoming director of the cancer center in 1993.

In 1983 he won the USC Associates Award for Creativity in Research and Scholarship. He is the author of more than 200 journal publications and book chapters, and he serves on several national and international committees, panels and editorial boards. He has received a variety of honors, including the Outstanding Investigator Grant from the National Cancer Institute and, in 1999, he was named distinguished professor of biochemistry and molecular biology at USC.

Five new members were elected to the AACR Board of Directors for the 2006-2009 term. They are:

James L. Abbruzzese, M.D., F.A.C.P. is the M. G. and Lillie A. Johnson Chair for Cancer Treatment and Research and Chairman of the Department of Gastrointestinal Medical Oncology at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. His research interests center on pancreatic and other gastrointestinal cancers, new drug development, non-invasive assessment of anti-cancer drug effects, and cancer prevention.

Born in Hartford, Conn., Abbruzzese graduated with honors from the University of Chicago, Pritzker School of Medicine. He completed residency in Internal Medicine at The Johns Hopkins Hospital in Baltimore Md., and a fellowship in Medical Oncology at the Dana-Farber Cancer Center, Harvard Medical School, Boston, Mass.

He is a deputy editor of the AACR journal Clinical Cancer Research. His past and present AACR committee service includes the areas research funding, clinical cancer research and a number in education and career development. He is active in program planning for international conferences and meetings, and has been a member of the faculty for the Scientist↔Survivor Program at four previous annual meetings.

Lucile L. Adams-Campbell, Ph.D. is director of the Howard University Cancer Center, in Washington, D.C., and professor of medicine, graduate professor of psychology and associate professor of physiology and biophysics at Howard University. Currently, she is the only African-American woman directing a cancer center in the United States. She is also visiting professor of oncology at Johns Hopkins University and adjunct professor of epidemiology at the University of Pittsburgh Graduate School of Public Health.

Her research primarily addresses health disparities related to women’s health issues, particularly breast cancer, with a focus on cancer etiology of disease outcomes attributed to exercise, nutrition and other lifestyle factors. In addition, as the principal investigator of a Minority Based Community Clinical Oncology Program, Adams-Campbell is actively involved in clinical trials in minority populations.

She received a B.S. in biology in 1977, and a M.S. in biomedical science in 1979, both from Drexel University in Philadelphia. In 1983, she became the first African-American woman in the country ever to receive a Ph.D. in epidemiology, when she earned her doctorate from the Graduate School of Public Health at the University of Pittsburgh.

Adams-Campbell chaired the AACR Minorities in Cancer Research Council between 2001 and 2004, and previously chaired the Minority Issues Committee for five years. She has served on the scientific review committee for two AACR International Conferences on Frontiers in Cancer Prevention Research. Her AACR committee memberships include Science Policy and Legislative Affairs, Science Education, Public Education and Annual Meeting Planning, among others.

Elizabeth H. Blackburn, Ph.D. is Morris Herzstein Professor of Biology and Physiology; professor of biochemistry and biophysics; and professor of microbiology and immunology with the University of California, San Francisco. For more than a quarter century, she has been investigating the structure and role of telomeres, the tips of genetic material at the end of chromosomes. She applies her insights into telomere biology to the development of a new anti-cancer therapy that forces cells with active telomerase to make errors during telomere synthesis, effectively triggering cellular suicide.

She earned B.Sc. and M.Sc. degrees in biochemistry from the University of Melbourne in Australia, and a Ph.D. in molecular biology from the University of Cambridge in England. Prior to joining the Department of Microbiology and Immunology at UCSF in 1990, she was a member of the molecular biology faculty at the University of California, Berkeley. She is a Non-Resident Fellow of the Salk Institute.

Blackburn received the Kirk A. Landon-AACR Prize for Basic Cancer Research in 2005. She also is a past winner of the Pezcoller-AACR International Award for Cancer Research, and the AACR-G.H.A. Clowes Memorial Award.

She is senior editor of the AACR journal Molecular Cancer Research. She co-chaired AACR special conferences on “The Role of Telomeres and Telomerase in Cancer,” in 2002 and 2004.

David R. Parkinson, M.D. is Vice President, Oncology Development and Commercialization at Amgen, Inc., in Thousand Oaks, Calif. He is responsible for devising strategic approaches to the development and commercialization of new oncology therapeutics, and serves as a member of Amgen’s Pipeline Steering Committee. Previously, he was global head of oncology translational development at Novartis Pharmaceutical Corporation, where he led teams that successfully registered numerous therapies internationally, including Gleevec®, the first successful protein kinase inhibitor, Zometa®, a bisphosphonate indicated for the treatment of bone metastases, and Femara®, an aromatase inhibitor indicated in the treatment of breast cancer.

Born in Canada, Parkinson received his M.D. degree from the University of Toronto School of Medicine in 1974, and did his residency in internal medicine at McGill University. He held academic positions at Tufts University School of Medicine in Boston, Mass., and The University of Texas M. D. Anderson Cancer Center in Houston, before moving to the National Cancer Institute in 1990, first as the head of the Biologics Evaluation Section of the Investigational Drug Branch, Cancer Therapy Evaluation Program, then as Chief of the Investigational Drug Branch of CTEP, and finally as Acting Associate Director of CTEP from 1995 until he left to join Novartis in 1997.

Parkinson currently serves the AACR as chairman of the Finance Committee and a member of the Publications Committee. He co-chairs the program committee for the AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development. Previous AACR service includes membership on the Task Force on Cancer Prevention and several award and program development committees.

Helen M. Piwnica-Worms, Ph.D. is professor of internal medicine and professor of cell biology and physiology at Washington University School of Medicine in St. Louis, Mo. She is also a Howard Hughes Medical Institute investigator. She is interested in how the cell division cycle is regulated and how perturbations in cell cycle control contribute to human cancer.

A graduate of St. Olaf College in Northfield, Minn., Piwnica-Worms earned a B.A. in biology in 1979. Her doctorate in microbiology and immunology is from Duke University in Durham, N.C. She took postdoctoral training at Harvard Medical School and Dana-Farber Cancer Institute in Boston, where she went on to become an instructor of pathology. She was assistant professor of physiology at Tufts University Medical School, also in Boston, and held assistant professorships in microbiology and molecular genetics at Harvard Medical School and Beth Israel Hospital.

She is currently senior editor of the AACR journal Molecular Cancer Research, and was co-chairperson of the AACR Annual Meeting Program Committee in 2005.

Four new members were elected to the AACR Nominating Committee. 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. They are:

Mina J. Bissell, Ph.D., senior advisor to the laboratory director on biology, and distinguished scientist, Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley.

Edison T. Liu, M.D., executive director of the Genome Institute of Singapore; executive director of the Singapore Tissue Network; executive director of the Singapore Cancer Syndicate; professor of medicine and professor of the department of Community, Occupational and Family Medicine, National University of Singapore.

Charles J. Sherr, M.D., Ph.D., Herrick Foundation Endowed Chair, Department of Genetics and Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, Tenn., and Howard Hughes Medical Institute investigator.

Craig B. Thompson, M.D., scientific director, Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center; chair of the Department of Cancer Biology and professor of medicine, University of Pennsylvania, Philadelphia.

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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. Our members include more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 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, and funding meritorious research projects. The AACR Annual Meeting attracts some 16,000 participants who share the latest discoveries and developments. Special Conferences throughout the year present novel information across a wide variety of cancer research and patient care topics. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention, as well as CR, a magazine about people and progress in cancer.

Contact:

Elizabeth Tait
2150440-9300 ext. 144
tait@aacr.org

Robert A. Weinberg and Angela M. Hartley Brodie Awarded 2006 Landon-AACR Prizes for Cancer Research

registration@aacr.org () — Tue, 28 Feb 2006 12:00:00 GMT

PHILADELPHIA – Two researchers whose pivotal discoveries have advanced progress against cancer by revealing vital information about the nature, origins and treatment of the disease are being honored with the 2006 Landon-AACR Prizes for Basic and Translational Cancer Research.

These prizes, offered by the Kirk A. and Dorothy P. Landon Foundation and the American Association for Cancer Research, are the largest awarded to cancer researchers by a professional society of their peers. Each winner will receive an unrestricted cash award of $200,000, and will present successive scientific lectures at the AACR Annual Meeting, in Washington, D.C., beginning at 4:30 p.m. on Monday, April 3, 2006, in Hall D of the Washington Convention Center.

This year’s Landon Prize recipients are:

Robert A. Weinberg, Ph.D., a founding member of the Whitehead Institute for Biomedical Research, and professor of biology at Massachusetts Institute of Technology, both in Cambridge, Mass., who will receive the 5th Kirk A. Landon-AACR Prize for Basic Cancer Research; and

Angela M. Hartley Brodie, Ph.D., professor of pharmacology and experimental therapeutics at the University of Maryland School of Medicine in Baltimore and University of Maryland Marlene and Stewart Greenebaum Cancer Center researcher, who will be awarded the 5th Dorothy P. Landon-AACR Prize for Translational Cancer Research.

“These extraordinary scientists have spent their careers working to unravel at the molecular level some of cancer’s most elusive mysteries,” said Margaret Foti, Ph.D., M.D. (h.c.), Chief Executive Officer of the AACR.

“Each has spent more than 30 years in the laboratory, pursuing with relentless dedication their theories about cancer’s mechanisms of invasion and progression in the complex chemistry of the human body,” Dr. Foti added. “Their insights, creativity and determination have saved lives and paved new pathways of investigation for other cancer scientists to pursue. They have also been exemplary teachers and mentors of the next generation of cancer researchers. We are proud to recognize their accomplishments with these major prizes.”

Robert Weinberg’s major contribution to the groundbreaking discovery of human oncogenes—genes that cause cancer when mutated—started with a simple question: How does cancer begin?

“If one looks at a human tumor, one realizes it’s a conglomerate of many cells which are growing, multiplying out of control,” Dr. Weinberg told the “NewsHour with Jim Lehrer” on July 28, 1999. On that day, the British journal Nature published the report by Dr. Weinberg and his research team of their successfully converting normal human cells into tumor cells in a culture dish.

“Looking inside the cells,” he continued “we identified a number of damaged genes, called oncogenes or tumor suppressor genes. They're the regulators that orchestrate the proliferation of the cell. For many years, we've been trying to figure out how these damaged genes force a normal cell to become a tumor cell. The problem, however, is that if one looks at human tumor cells, as isolated from patients, these cells have an unknown number of damaged genes, and so we've been hard-pressed to enumerate all of the genetic damage that is required to convert a normal human cell into a cancer cell, into a tumor.”

Dr. Weinberg and his colleagues built upon the previous discovery of telomeres, specialized structures that define the ends of chromosomes. Every time a cell divides, the DNA at each telomere gets shorter. The enzyme responsible for maintaining telomere length, called telomerase, occurs at low levels in normal human tissues. In tumor cells, telomerase is more prevalent and more active, giving cells a longer than normal life span, that is, more time to replicate and grow.

The genes coding for telomerase proved to be the essential ingredients in the molecular cocktail which must be altered within a cell before it is transformed from the normal state to cancer. Once the Weinberg team learned the identities of the genes critical to tumor formation, they were able to effect the transformation in vitro. The search for the formula required to transform normal human cells into cancer cells took more than 15 years.

The Weinberg Lab continues to study the molecular mechanisms that control the growth of human tumors and their ability to seed distant growths—metastases. This work has revealed ways in which normal stromal (connective tissue) cells recruited into a tumor aid the growth and survival of the cancer cells. In addition, by studying genes that are normally active early in embryonic development, Dr. Weinberg and his colleagues have discovered mechanisms by which cancer cells in a primary tumor acquire the ability to invade nearby tissues and to spread to distant sites in the body.

“Cancer research has been a consuming passion of my life for three decades, and so it comes as an extraordinary honor that I am recognized in this way by my peers who include, by all measures, the world leaders in this dynamic and ever-fascinating field of science,” said Dr. Weinberg. “I am extremely flattered. Never in my wildest dreams could I have imagined that my work begun three decades ago would lead to recognition of this sort.”

Angela M. Hartley Brodie is being honored for discovering and developing a new class of drugs called aromatase inhibitors, which help prevent the recurrence of breast cancer in postmenopausal women. The drug works by interfering with aromatase—the enzyme that catalyzes the key step in the biosynthesis of estrogens—thereby stopping the production of the hormone that fuels the growth of cancer cells. Other drugs for the treatment of breast cancer, such as tamoxifen, block estrogen from binding to the estrogen receptors in cancer cells. Many breast cancers are hormone-dependent, requiring estrogen to reproduce and grow.

Dr. Brodie’s interest in the role of estrogens in breast cancer arose early in her career while she was working as a research assistant in the Department of Hormone Research at the Christie Hospital in Manchester, U.K. Some 15 years later, in 1973, while a staff scientist at the Worcester Foundation for Experimental Biology in Shrewsbury, Mass., Dr. Brodie and her husband reported a number of compounds that are selective inhibitors of aromatase. They hypothesized that aromatase inhibitors might be better alternatives than tamoxifen, a weak antiestrogen which produces a slight estrogenic effect. Consequently, tumors are not always suppressed by tamoxifen; moreover, the drug no longer works after five years and increases the risk of strokes and endometrial cancer.

It was in 1982 when Dr. Brodie collaborated with colleagues in her native England to treat breast cancer patients with the aromatase inhibitor that had proved to be most potent in her studies. The compound 4-hydroxyandrostenedione (4-OHA) was synthesized in Dr. Brodie’s laboratory at the University of Maryland School of Medicine in Baltimore, and her collaborators at the Royal Marsden Hospital in London successfully arrested tumors in women whose breast cancer was resistant to tamoxifen and other standard treatments.

After further trials, 4-OHA was introduced on the market as formestane in 1994. It was the first new treatment for breast cancer in a decade. Today, three aromatase inhibitors are approved for use by women with estrogen receptor positive metastatic breast cancer.

“Bringing a new discovery from the laboratory into the clinic is a long, involved process,” Dr. Brodie told a writer for the University of Maryland Marlene and Stewart Greenebaum Cancer Center Website last year.

“In the beginning, the scientific community was convinced that this new approach wouldn’t work, that antiestrogens like tamoxifen were the only way to go,” added Dr. Brodie, who was awarded the 2005 Charles F. Kettering Prize in recognition of her work. “We tried to interest a number of drug companies in developing these new compounds, but new drug development is a risky business and they were not terribly interested. It wasn’t until we began conducting clinical trials with my colleagues in London on our compound formestane, and showing positive results in patients, that we were able to interest the pharmaceutical companies in developing this class of agents.”

These studies and current clinical trials show aromatase inhibitors to be more effective than tamoxifen in first-line therapy and, more recently, in preventing breast cancer recurrence in women who received a five-year course of tamoxifen. Dr. Brodie is applying similar approaches to develop novel agents for treating prostate cancer. Inhibitors targeting the enzymes that synthesize the male hormone androgen and its receptors are in development.

“To be selected for the Landon-AACR Prize for Translational Cancer Research is a tremendous honor, and I am very grateful to receive this recognition of my work,” Dr. Brodie said. “I am very happy indeed that our work turned out to be beneficial for breast cancer patients.”

Editors Note: Photographs of Robert A. Weinberg and Angela M. Hartley Brodie can be downloaded here and here. A concurrent release is being issued by the University of Maryland School of Medicine.

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Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract nearly 16,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.

The Landon-AACR Prizes for Basic and Translational Cancer Research were launched in the summer of 2002 to promote recognize and reward seminal contributions to our understanding of cancer through basic and translational cancer research. These distinguished scientific prizes bring heightened public attention to landmark achievements in the continuing effort to prevent and cure cancer through high-quality laboratory and translational cancer research.

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:

Elizabeth Tait
215-440-9300 ext. 144
tait@aacr.org

Funding for Colon Cancer Research Available

registration@aacr.org () — Mon, 27 Feb 2006 12:00:00 GMT

Applications Open for The Jeannik M. Littlefield-American Association for Cancer Research Grants in Metastatic Colon Cancer Research

Application Deadline: Monday, March 27, 2006

PHILADELPHIA—The AACR and the Littlefield 2000 Trust have entered into a new partnership to establish the Jeannik M. Littlefield-AACR Grants in Metastatic Colon Cancer Research. Support of $100,000 to $250,000, over one or two years, is available for innovative research projects designed to accelerate the discovery and development of new agents to treat metastatic colon cancer. Proposals that focus on pre-clinical research with direct therapeutic intent also will be accepted. Special emphasis will be placed on promising research for individualized treatments or other novel cancer therapeutics which will translate into clinical applications within a one- to two-year period.

Applications for the first Jeannik M. Littlefield-AACR Grants in Metastatic Colon Cancer Research are due by Monday, March 27, 2006.

Researchers who are affiliated with any institution involved in cancer research, cancer medicine, or cancer-related biomedical science anywhere in the world may apply.

The grants are sponsored by Jacques and Sandy Littlefield, of Portolo Valley, Calif., who donated $3 million to the AACR at the end of last year. They are named for Mr. Littlefield’s mother.

“Ensuring an adequate and expertly trained cancer research workforce for the future has always been an integral part of the AACR’s mission, and never more so than now, as we stand on the threshold of our second century,” noted David Irwin, Ph.D., Managing Director of the association’s Science and Education Division.

“These new grants add considerably to our existing program of scientific awards, travel grants and research funding, and set a strong precedent for more privately supported, disease-specific cancer research in an era of changing national funding priorities,” said Irwin.

Applications will be evaluated by a selection committee comprised of at least seven well- respected and highly accomplished senior scientists.

The Littlefield-AACR Grants Scientific Review Committee will consider each application independently, based on the following criteria:

extent to which the proposed study addresses an important problem related to metastatic colon cancer;
degree to which the studies will impact the understanding and treatment of gastrointestinal malignancies;
whether the studies are designed appropriately to provide answers to the research questions posed;
originality and level of innovation;
research credentials of the investigative group; and
contribution of the institutional environment to the probability of success of the proposed studies.

In order to be eligible, researchers must have acquired a doctoral degree in a related field. If an applicant has obtained an equivalent degree at a foreign institution, information on the nature of the degree must be provided at the time of application.

Applicants need not be members of the AACR. However, grant recipients will be expected to become AACR members following presentation of the grants.

There are no geographic, national, or residency status restrictions.
For more information, visit the AACR website at http://www.aacr.org/page5528.aspx. To apply, visit the proposalCENTRAL website at http://v2.ramscompany.com.

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Contact:

Elizabeth Tait
215-440-9300 ext. 144
tait@aacr.org

Botox Could Help Target Resistant Tumors for Treatment

registration@aacr.org () — Wed, 15 Feb 2006 12:00:00 GMT

PHILADELPHIA – The cosmetic treatment Botox may have a new use as an adjuvant to cancer therapy, providing an open door for chemotherapy and radiation treatments, according to a study published in the Feb. 15 issue of Clinical Cancer Research.

The study in mice, led by Bernard Gallez, Ph.D., professor of pharmacy at the Université de Louvain in Brussels, Belgium, found that by injecting Botulinum neurotoxin type A into two types of mouse tumors, the tumors’ cellular vasculature opened, allowing for more effective destruction of previously resistant cancer cells. The study is the first to test the idea of using Botox against cancer and explores the possibility of its use as an adjuvant, assisting the effective delivery of chemotherapies and radiation.

The findings mark a relatively new area of cancer research, which focuses on briefly opening blood vessels that feed tumor cells in order to better deliver therapeutic agents. Until recently, much cancer research has focused on the opposite: reduction of blood vessel growth, which starves tumor cells of nutrients.

“Tumor vasculature is targeted by several advanced anti-cancer approaches that may appear contradictory,” said Gallez. “Anti-angiogenesis and anti-vascular targeting are methods aimed at destroying the vessels that feed tumors, thereby depriving them of oxygen and nutrients.

“In contrast, pro-vascular approaches increase tumor perfusion and oxygenation temporarily.”

While chemotherapy and radiation treatments have remained the standard of care, tumor cells of most cancer types have shown the ability to develop resistance to therapies. This phenomenon has resulted in more toxic dosages of chemotherapy and radiation, and increased efforts to develop more drugs to which tumors don’t show resistance. To increase the efficacy of anti-cancer treatments, the new study examined strategies that transiently opened the tumor vascular bed to alleviate tumor hypoxia.

“Hypoxia is a source of resistance to radiotherapy, and is a determining factor in the poor prognosis of tumors to cytotoxic treatments,” said Gallez. “Botulinum toxin could lead to inhibition of contractions of tumor vessels, improve tumor perfusion and oxygenation, and enhance the response of tumors to radio- and chemotherapy.”

Botulinum toxin is a naturally occurring molecule, and historically has been implicated with intestinal poisonings. It has been developed for several clinical applications, including facial spasms, strabismus (a disease of the eye muscles), and other muscle hyperactivity. It also has become popularly known as Botox for its cosmetic uses on the face.

The toxin acts on the nervous system by blocking the release of neurotransmitters, particularly acetylcholine and norepinephrine. Gallez and his colleagues hypothesized that since Botulinum toxin impeded neurotransmitter release in the sympathetic nervous system, it could prevent neuromuscular contractions of vessels in tumors. The inhibition of this contraction could literally open the gate to improved tumor perfusion by chemotherapeutic drugs and oxygenation that enhances radiotherapy.

The scientists used two tumor models, one for fibrosarcoma and the other for mouse liver tumor. Botox was injected into the tumor once it had grown to about 6 mm. The tumors were then examined for three days, for vascular and perfusion changes as well as responses to anti-cancer therapies. In tests on oxygenation, cellular oxygen pressure was shown to significantly increase after treatment by Botox in both types of tumors. In tests on perfusion, magnetic resonance imaging results (MRI) showed significantly greater perfusion in treated mice after three days.

In addition, Botox “pre-treatment” led to significantly greater delays in tumor growth as well as stimulation of apoptosis (programmed cellular death) when compared by irradiation without Botox. The combination of Botox and the chemotherapeutic agent cyclophosphamide showed significantly stunted tumor growth after three days, as well.

Since Botox is used in clinics without serious toxicity, the study indicates the possibility for human trials. In addition, dosages used in the mouse study were within the range used with humans in clinical settings. The toxin is administered inside the tumor with very limited diffusion into normal tissues, which may limit the amount of damage to normal cells in proximity to the tumor.

“This is the first experimental model demonstrating how Botox can affect the reaction of blood vessels that feed tumors,” said Gallez. “Tumor microvessels are formed hastily, and lack smooth muscle layers, but one can find mature blood vessels, with smooth muscle layers that respond to toxins like Botulinun, inside tumors. Several laboratories, including ours, are working on new strategies to alleviate tumor hypoxia, which sensitizes the tumor to treatment. Botox appears to offer the advantage of selectivity, absence of toxicity and persistence for a longer time than other agents that act on tumor vasculature. Further research may help us determine whether this approach would be useful to treating cancer in humans.”

The Gallez study was conducted by Réginald Ansiaux, Christine Baudelet, Greg Cron, Jérôme Segers, Chantal Dessy, Philippe Martinive, Julie De Wever, Julien Verrax, Valérie Wauthier, Nelson Beghein, Vincent Grégoire, Pedro Buc Calderon, and Olivier Feron, all of the Université de Louvain.

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Contact:
Russell Vanderboom, Ph.D.
215-440-9300 ext. 120
vanderboom@aacr.org

AACR Supports New FDA Clinical Research Guidelines

registration@aacr.org () — Thu, 12 Jan 2006 12:00:00 GMT

PHILADELPHIA -- The American Association for Cancer Research, the world’s oldest and largest organization dedicated to cancer research, enthusiastically supports the new guidelines announced today by the U.S. Food and Drug Administration, whose primary goal is to streamline the earliest phases of clinical research for new medical treatments.

As described, the new guidelines are in keeping with FDA’s Critical Path Initiative designed to accelerate the approval of innovative diagnostics, drugs and other therapeutics to prevent and treat diseases, including cancer.

“All of the nation’s cancer research community has been talking excitedly about ‘translational’ cancer research, the process by which new discoveries about cancer are developed for human use in cancer detection, diagnosis, prevention and treatment,” said William G. Nelson V, M.D., Ph.D., AACR’s chairperson of the Science Policy and Legislative Affairs Committee and professor of Oncology, Urology, Pharmacology, Medicine, Pathology and Radiation Oncology at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“The new FDA guidelines address critical issues in translational research, providing defined pathways for introducing the latest innovations for cancer into human clinical trials, and attempts to modernize standards across clinical sites,” he added.

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Media Contact:
Warren R. Froelich
215/440-9300, Ext. 198
froelich@aacr.org