AACR Press Releases

American Association for Cancer Research CEO Recognized With Prestigious Award From Fox Chase Cancer Center

registration@aacr.org () — Thu, 16 May 2013 12:00:00 GMT

PHILADELPHIA — Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer (CEO) of the American Association for Cancer Research (AACR), was honored with the 2013 Stanley P. Reimann Honor Award for her deep and far-reaching contributions to cancer science and medicine at a celebration hosted by Fox Chase Cancer Center, held last night in Philadelphia, Pa.

“I am deeply honored and humbled to receive the 2013 Stanley P. Reimann Honor Award,” said Foti. “Dr. Riemann was a true pioneer in the cancer research community. His vision and commitment to discovery and collaborative science continue to define the cutting-edge research program conducted at the Fox Chase Cancer Center. Dr. Reimann’s vision of building purposeful coalitions to foster the exchange of new knowledge among cancer researchers is central to accelerating advances in the field and to saving more lives.”

The Stanley P. Reimann Honor Award is bestowed by Fox Chase Cancer Center to individuals from different spheres of influence who bring exceptional ingenuity and expertise to the cancer cause. Previous awardees include Nancy Brinker, C. Everett Koop, Frank Rauscher Jr. and Baruch S. Blumberg. The award was established in 1974 to perpetuate the memory of Stanley P. Reimann, M.D., the founder of the Institute for Cancer Research, which merged with the American Oncologic Hospital to form Fox Chase Cancer Center in 1974.

Foti became CEO of the AACR in 1982. Working collaboratively with the elected officers of the AACR, she has provided the continuity of leadership that has been critical to the association’s progress and its mission to prevent and cure cancer. During her tenure, the AACR’s membership has grown from about 3,000 to 34,000 laboratory, translational and clinical researchers; health care professionals; students; cancer survivors; and research and patient advocates in the United States and more than 90 other countries.

Foti’s efforts to accelerate the dissemination of new research findings among scientists and others dedicated to the conquest of cancer have included the launch of seven peer-reviewed scientific journals: Cancer Discovery; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; Cancer Prevention Research; and Cancer Immunology Research. Her leadership also has been instrumental in expanding the AACR’s comprehensive program of national and international conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees, to increase the pace of progress in understanding cancer biology, diagnosis, treatment and prevention.

In addition, Foti leads the AACR’s scientific partnership with Stand Up To Cancer, a charitable initiative that supports groundbreaking research aimed at getting new cancer treatments to patients in an accelerated time frame. The AACR plays an integral role by providing expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit.

Foti has received many national and international honors and awards for her contributions to cancer research. Most recently, she was honored with the Mildred Scheel Lectureship, which was established by the German Cancer Research Center and the German Cancer Aid to acknowledge women dedicated to the advancement of cancer research. Earlier this year, she was recognized with the Distinguished Partner in Hope Award during the Annual Colorectal Cancer Conference hosted by the Abramson Cancer Center of the University of Pennsylvania in Philadelphia. In 2012, she received the National Brain Tumor Society’s Founders Award for Excellence in Cancer Research, was recognized as a “First Lady” of the Intercultural Cancer Council, received the Biotechnology Industry Organization’s 2012 Biotech Humanitarian Award and received Research!America’s 2012 Raymond and Beverly Sackler Award for Sustained National Leadership.

She has received numerous other accolades, such as the first Margaret Foti Award, which was established in cooperation with the University of Catania Ph.D. Oncology Program and the Italian League Against Cancer of Catania; the first Margaret Kripke Legend Award from The University of Texas MD Anderson Cancer Center; the European CanCer Organization Lifetime Achievement Award; and a citation from Philadelphia Mayor Michael Nutter for her dedication to increasing awareness of the importance of cancer research, as well as for her pivotal role in designating May as National Cancer Research Month. Foti was also the first recipient of an AACR award created in her name in 2007. She holds three honorary doctorates in medicine and surgery from medical institutions in Italy and Spain.

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Sleep Problems May Increase Risk for Prostate Cancer

registration@aacr.org () — Tue, 07 May 2013 12:00:00 GMT

Problems falling asleep and staying asleep increased risk for prostate cancer.
The association was stronger for advanced disease.
Larger studies with longer follow-up are necessary for confirmation.

PHILADELPHIA — Men who reported sleep problems, including difficulty falling asleep and staying asleep, had up to a twofold increased risk for prostate cancer, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Sleep problems are very common in modern society and can have adverse health consequences,” said Lara G. Sigurdardóttir, M.D., at the University of Iceland in Reykjavik. “Women with sleep disruption have consistently been reported to be at an increased risk for breast cancer, but less is known about the potential role of sleep problems in prostate cancer.”

Previous studies have generated conflicting results for an association between sleep disruption from working night shifts and the risk for prostate cancer. Sigurdardóttir and her colleagues, therefore, investigated the role of sleep in influencing prostate cancer risk.

The researchers followed 2,102 men from the prospective Age, Gene/Environment Susceptibility-Reykjavik study, which involved an established, population-based cohort of 2,425 men aged 67 to 96. Upon enrollment into the study, the participants answered four questions about sleep disruption: whether they took medications to sleep, had trouble falling asleep, woke up during nights with difficulty going back to sleep or woke up early in the morning with difficulty going back to sleep.

Among the participants, 8.7 percent and 5.7 percent reported severe and very severe sleep problems, respectively. None of the participants had prostate cancer at study entry. The researchers followed the participants for five years, and during this period, 6.4 percent were diagnosed with prostate cancer.

After the researchers adjusted for age, they found that compared with men who reported no problems with sleeping, the risk for prostate cancer increased proportionately with reported severity of problems falling and staying asleep, from 1.6-fold to 2.1-fold. Further, the association was stronger for advanced prostate cancer than for overall prostate cancer, with more than a threefold increase in risk for advanced prostate cancer associated with “very severe” sleep problems.

To rule out the possibility that the problems with sleeping were because of undiagnosed prostate cancer or an enlarged prostate, the researchers reanalyzed the data after excluding men with symptoms of sleep disturbance that might be indicative of nocturia (waking up during the night to urinate). The results remained unchanged.

According to Sigurdardóttir, these data should be confirmed with a larger cohort with longer observation times. “Prostate cancer is one of the leading public health concerns for men and sleep problems are quite common,” she said. “If our results are confirmed with further studies, sleep may become a potential target for intervention to reduce the risk for prostate cancer.”

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Exercise-related Changes in Estrogen Metabolism May Lower Breast Cancer Risk

registration@aacr.org () — Tue, 07 May 2013 12:00:00 GMT

Physical activity may reduce breast cancer risk by altering estrogen metabolism.
Women who did aerobic exercises had an increased ratio of “good” to “bad” metabolites of estrogen.

PHILADELPHIA — Changes in estrogen breakdown, or metabolism, may be one of the mechanisms by which aerobic exercise lowers a woman’s breast cancer risk, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Observational studies suggest physical activity lowers breast cancer risk, but there are no clinical studies that explain the mechanism behind this,” said Mindy S. Kurzer, Ph.D., professor in the Department of Food Science and Nutrition at the University of Minnesota in Saint Paul. “Ours is the first study to show that aerobic exercise influences the way our bodies break down estrogens to produce more of the ‘good’ metabolites that lower breast cancer risk.”

Kurzer and her colleagues conducted the Women in Steady Exercise Research (WISER) clinical trial, which involved 391 sedentary, healthy, young, premenopausal women. They randomly assigned the women to two age-matched, body mass index-matched groups: a control group of 179 women and an intervention group of 212 women.

While women in the control group continued a sedentary lifestyle for the entire study period, women in the intervention group performed 30 minutes of moderate-to-vigorous aerobic exercise five times a week for 16 weeks. Aerobic exercises included the treadmill, stair stepper or elliptical machine. The researchers adjusted the workout intensity for each individual so that the maximal heart rate was uniform among all participants.

Eighty-six percent of participants from the control group and 78 percent from the intervention group completed the study.

The researchers collected 24-hour urine samples on three consecutive days prior to study initiation and on three consecutive days at the end of the study. Using a state-of-the-art technique called liquid chromatography/tandem mass spectroscopy, they measured the amount of three parent estrogens, E₁, E₂ and E₃, and nine of their breakdown products called metabolites, in the participants’ urine samples. According to Kurzer, estrogen metabolism favoring the production of a metabolite called 2-hydroxyestrone (2-OHE₁) over one called 16alpha-hydroxyestrone (16alpha-OHE₁), which results in an increase in the 2-OHE₁/16alpha-OHE₁ ratio, has been linked with a reduction in breast cancer risk.

She and her colleagues found that aerobic exercise led to an increase in the amount of 2-OHE₁ and a decrease in the amount of 16alpha-OHE₁, which led to a significant increase in the 2-OHE₁/16alpha-OHE₁ ratio. There were no changes in the 2-OHE₁/16alpha-OHE₁ ratio in the urine of control group participants.

“Exercise, known to favor fitness and improve heart health, is also likely to help prevent breast cancer by altering estrogen metabolism,” said Kurzer. “It is very important, however, to decipher the biological mechanisms behind this phenomenon.”

In collaboration with researchers at the University of Pennsylvania in Philadelphia, Kurzer is conducting similar studies in women with a high risk for breast cancer.

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AACR Opposes Bill to Exempt Cigars From FDA Regulation

registration@aacr.org () — Wed, 01 May 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) formally issued letters to all members of the House of Representatives and the Senate urging them to oppose recently introduced legislation that would exempt many cigars from regulation.

The Food and Drug Administration (FDA) currently regulates cigarettes, smokeless tobacco and roll-your-own cigarette tobacco, and has signaled that it intends to exercise its authority over cigars this year.

The “Traditional Cigar Manufacturing and Small Business Jobs Preservation Act of 2013,” H.R. 792 and S. 772, will create a new classification of cigars and exempt them from FDA oversight.

“Cigars, like cigarettes, are addictive and carcinogenic; the evidence is clear,” stated Margaret Foti, Ph.D., M.D. (h.c.), AACR chief executive officer. “The idea that we should treat cigars differently from other dangerous tobacco products would be a step backward in protecting the health of our nation.”

Cigar use has increased significantly over the past decade, posing a threat to all Americans, especially to children. The AACR’s letters express concern for the increasing prevalence of youth cigar use, and point out that under the proposed legislation cigar manufacturers could continue to add candy flavorings to cigars, increasing their appeal. Bans on candy flavoring are among the restrictions placed by the FDA on cigarettes, and the FDA is expected to extend similar restrictions to cigars this year.

The AACR’s letters also emphasize the significant economic burden tobacco use imposes on our society. The Centers for Disease Control and Prevention has estimated that in 2004 smoking cost the U.S. economy $193 billion in health costs, employee absenteeism and lost productivity.

“Tobacco use is implicated in nearly one in three cancer deaths and takes an enormous financial and health toll on this country,” said Roy Herbst, M.D., Ph.D., chief of medical oncology at Yale Comprehensive Cancer Center in New Haven, Conn., and chair of the AACR Tobacco and Cancer Subcommittee. “We are slowly getting the smoking rate down and reaping dividends in terms of reduced cancer incidence, but this legislation will threaten that progress.”

The AACR issued a 2010 policy statement on tobacco and cancer* that called for evidence-based regulation of tobacco products by the FDA. (*Adobe Acrobat Reader required)

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Women Smokers May Have Greater Risk for Colon Cancer Than Men

registration@aacr.org () — Tue, 30 Apr 2013 12:00:00 GMT

Smokers of both genders had increased risk for colon cancer compared with never-smokers.
The risk increase was greater for female smokers.
The more and longer a woman smoked, the greater her risk.

PHILADELPHIA — Smoking increased the risk for developing colon cancer, and female smokers may have a greater risk than male smokers, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Globally, during the last 50 years, the number of new colon cancer cases per year has exploded for both men and women,” said Inger Torhild Gram, M.D., Ph.D., professor in the Department of Community Medicine at the University of Tromsø in Norway. “Our study is the first that shows women who smoke less than men still get more colon cancer.”

Gram and her colleagues examined the association between cigarette smoking and colon cancer, by tumor location, in a large Norwegian cohort of more than 600,000 men and women. The participants from four surveys initiated by the National Health Screening Service of the Norwegian Institute of Public Health had a short health exam and completed questionnaires about smoking habits, physical activity and other lifestyle factors. The participants were followed by linkage to the Cancer Registry of Norway and the Central Population Register. During an average 14 years of follow-up, close to 4,000 new colon cancer cases were diagnosed.

Gram and colleagues found that female smokers had a 19 percent increased risk compared with never-smokers, while male smokers had an 8 percent increased risk compared with never-smokers.

In addition, women who started smoking when they were 16 or younger and women who had smoked for 40 years or more had a substantially increased risk, by about 50 percent. Also, the dose-response association between the number of cigarettes smoked per day, number of years smoked and number of pack-years smoked and colon cancer risk was stronger for women than it was for men.

“The finding that women who smoke even a moderate number of cigarettes daily have an increased risk for colon cancer will account for a substantial number of new cases because colon cancer is such a common disease,” said Gram. “A causal relationship between smoking and colorectal cancer has recently been established by the International Agency for Research on Cancer of the World Health Organization, but unfortunately, this is not yet common knowledge, neither among health personnel nor the public.”

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Obese Men With Benign Biopsy at High Risk for Prostate Cancer

registration@aacr.org () — Tue, 23 Apr 2013 12:00:00 GMT

Data on obesity and prostate cancer conflict.
Precancerous lesions were more common in benign biopsy specimens from obese men.
After benign biopsy, obese men at higher risk for future prostate cancer.

PHILADELPHIA — Obese men were more likely to have precancerous lesions detected in their benign prostate biopsies compared with nonobese men and were at a greater risk for subsequently developing prostate cancer, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Our study is focused on a large group of men who have had a prostate biopsy that is benign but are still at a very high risk for prostate cancer,” said Andrew Rundle, Dr.P.H., associate professor of epidemiology at Columbia University Mailman School of Public Health in New York, N.Y. “Studies conducted in the past have attempted to determine if there are subpopulations of men diagnosed with benign conditions that may be at a greater risk for developing prostate cancer. This is one of the first studies to assess the association between obesity and precancerous abnormalities.”

Rundle and his colleagues investigated the association between obesity and future prostate cancer incidence within a cohort of 6,692 men at the Henry Ford Health System who were followed for 14 years after a biopsy or transurethral resection of the prostate with benign findings. The investigation was part of a larger study of environmentally-induced tissue biomarkers for prostate cancer funded through a research grant awarded by the National Institutes of Health to Benjamin Rybicki, Ph.D., a research scientist at the Henry Ford Health System and the senior co-author of the study.

The researchers conducted a case-control study among 494 of these patients and 494 matched controls; they found precancerous abnormalities in 11 percent of the patients’ benign specimens. These abnormalities were significantly associated with obesity at the time of the procedure, according to Rundle.

After accounting for several variables, including family history of prostate cancer, prostate-specific antigen (PSA) levels during the initial procedure, and the number of PSA tests and digital rectal exams during follow-up, the researchers found that obesity at the time of the initial procedure was associated with a 57 percent increased incidence of prostate cancer during follow-up.

Rundle noted, however, that this association was only apparent for tumors occurring earlier in the follow-up period. “We don’t absolutely know what the true biology is,” said Rundle. “In some ways, this reflects the association between the body size and larger prostate size, which is thought to reduce the sensitivity of the needle biopsy. It is possible that the tumors missed by initial biopsy grew and were detected in a follow-up biopsy.”

The association observed between body size and prostate cancer risk is larger than that seen in prior studies, according to Rundle. He attributed the differences to the variables of the cohort, which was composed of men at high risk for prostate cancer. In addition, since these high-risk men were members of the Henry Ford Medical System, they underwent increased medical surveillance, which included repeated biopsy and regular PSA screening.

“We need some guidance on when or for whom a full follow-up is required,” said Rundle. “Obesity should be considered a factor for more intensive follow-up after a benign prostate biopsy.”

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Water-pipe Smoking May Not Be a Safe Alternative to Cigarette Smoking

registration@aacr.org () — Fri, 19 Apr 2013 12:00:00 GMT

Water-pipe smoking led to exposure to agents that may cause cardiovascular diseases and leukemia.
Comparison of cigarette and water-pipe smoking showed different patterns of exposure to tobacco toxicants.

PHILADELPHIA — Smoking tobacco in a water pipe resulted in a different pattern of exposure to toxic substances and may result in a cancer risk profile that is different from that of cigarette smoking, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Water-pipe smoking at ‘hookah bars’ has become popular with young people in the United States, and some believe that it is less harmful than cigarette smoking,” said Peyton Jacob III, Ph.D., a University of California, San Francisco research chemist at San Francisco General Hospital and Trauma Center. “We report for the first time that toxicant exposures from water-pipe and cigarette smoking differed in pattern, with higher exposure to some toxicants like carbon monoxide and benzene in water-pipe smokers.”

To compare the levels of exposure to various tobacco toxicants, Jacob and colleagues conducted a randomized study of 13 healthy volunteers, eight men and five women. All were experienced in smoking cigarettes and using water pipes. Because different individuals excrete different amounts of toxic chemicals even if they inhale the same amounts, the most straightforward way to compare exposures was to conduct a “cross-over” study, where the same person smoked cigarettes and a water pipe on different days, according to Jacob.

Volunteers either smoked cigarettes or a water pipe exclusively during the day for four days as inpatients at the San Francisco General Hospital. After a week or more each individual was readmitted to the hospital and switched to the other product for the next four days. On average, volunteers smoked three water-pipe sessions or 11 cigarettes per day. The researchers collected blood and urine samples before, during and at the end of each type of smoking session.

The researchers found that water-pipe smoking resulted in about half the amount of total nicotine measured in the blood during a 24-hour period compared with cigarette smoking. However, exposure to nicotine, albeit at lower levels, can sustain addiction, according to Jacob. On the other hand, the researchers found that while smoking a water pipe, the total amount of carbon monoxide in the breath measured during a 24-hour period was more than 2.5 times higher than while smoking cigarettes. Jacob explained that high carbon monoxide exposure increases the risk for acute events such as a heart attack, stroke or sudden death in people who have cardiovascular or lung diseases.

In addition, the data indicated that exposure to benzene, a volatile organic compound, was considerably higher while smoking a water pipe: The researchers detected twice the amount of a metabolite of benzene in the urine of water-pipe smokers compared with that of cigarette smokers. Jacob warned that benzene exposure is a concern because it is known to cause leukemia in humans.

“People want to know if it is a lesser health risk if they switch from cigarettes to smoking a water pipe on a daily basis,” said Jacob. “We found that water-pipe smoking is not a safe alternative to cigarette smoking, nor is it likely to be an effective harm reduction strategy.”

The researchers acknowledge that while sharing water pipes in social settings, the exposure to toxic agents may be lesser, and they are conducting further research to ascertain this.

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AACR-Minorities in Cancer Research Honors Dr. Gabriel Hortobagyi With Jane Cooke Wright Lectureship Award

registration@aacr.org () — Wed, 10 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) and its Minorities in Cancer Research membership group will award Gabriel N. Hortobagyi with the Jane Cooke Wright Lectureship at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

Hortobagyi is professor of medicine in the Department of Breast Medical Oncology and holds the Nellie B. Connally chair in breast cancer at The University of Texas MD Anderson Cancer Center in Houston. His award presentation and lecture, “Dual Targeting for Endocrine Therapy of Breast Cancer,” will take place on Sunday, April 7 at 4:15 p.m. ET in Ballroom C in the Walter E. Washington Convention Center.

“I’m humbled by the AACR and the Minorities in Cancer Research group. To be recognized for furthering the advancement of minority investigators in cancer research is truly an honor,” Hortobagyi said. “All of us share a mutual dedication to breast cancer care and feel that there has never been a more exciting time for the field.”

The AACR-MICR Jane Cooke Wright Lectureship was established in 2006 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.

Hortobagyi is known for his role in advancing novel agents for the treatment of breast cancer and also for his mentorship of minority investigators. Many of his key publications have been first-authored by minority junior investigators, showing his commitment to their development.

The lectureship is named in honor of Jane Cooke Wright, M.D., a pioneer in clinical cancer chemotherapy and an exceptional scientist who has made important contributions to research in this field, and who recently passed away at the age of 93. Wright, a member of the AACR since 1954, became the highest ranking black woman at a nationally recognized medical institution in 1967, at a time when there were only a few hundred black, female physicians in the United States. She attended the AACR Annual Meeting each year since the lectureship’s establishment in order to provide opening remarks and introduce the year’s lecturer. She was elected this year into the inaugural class of the Fellows of the AACR Academy. For more information on Wright, please visit www.aacr.org/JCW_Memoriam.

“I had the distinct pleasure of knowing Jane Cooke Wright. Her myriad scientific contributions and unwavering commitment to mentoring young scientists, especially African-American women, are still impactful in cancer research and the community at large,” Hortobagyi said.

Hortobagyi is an AACR member who has served on the editorial board of Clinical Cancer Research, as co-chair of the Research Grant Review Committee and as a member of the San Antonio Breast Cancer Symposium Komen Award Committee and the Clinical Research and Experimental Therapeutics Awards Committee.

He has received many honors throughout his career, including the Brinker International Award for Clinical Research, the Bristol-Myers Squibb Horizon Scientific Award and the Glen Robbins Award in Breast Cancer Research from the New York Cancer Society and the Metropolitan Breast Cancer Group. Last year, he received the Jill Rose Award from the Breast Cancer Research Foundation and the William L. McGuire Award at the CTRC-AACR San Antonio Breast Cancer Symposium. Additionally, Hortobagyi was named the 2005 World Leader in Oncology from the Mexican Society of Oncology and Chevalier of the Order of la Legion d’Honneur de France by President Jacques Chirac. He is also a past-president of the American Society of Clinical Oncology.

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Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
lauren.riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

More Than $5 Million in Research Grants Awarded by the Pancreatic Cancer Action Network and AACR

registration@aacr.org () — Wed, 10 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The Pancreatic Cancer Action Network and the American Association for Cancer Research (AACR) awarded 14 grants totaling more than $5 million to outstanding scientists throughout the country, supporting their innovative research in the field of pancreatic cancer. In an effort to speed advances in the field, the organizations have awarded two Inaugural Research Acceleration Network (RAN) grants totaling $1 million each.

This year’s total funding level represents the largest annual disbursement since the Pancreatic Cancer Action Network introduced the program in 2003. To date, the organization has awarded 94 research grants to researchers at institutions around the country totaling nearly $18 million. This year’s recipients will be honored at a grants reception and dinner during the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“The AACR is delighted to be partnering once again with the Pancreatic Cancer Action Network,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “It continues to be a pleasure to work with its President and CEO Julie Fleshman and other dedicated staff on the scientific review and administration of grants that fund cutting-edge research projects with the potential to lead to major breakthroughs that will prevent, detect and treat pancreatic cancer, one of the most deadly of cancers. We are especially excited about the Research Acceleration Network grants, as they are new grants promoting the kind of collaborations that are vital to accelerating research progress.”

Pancreatic cancer is the fourth leading cause of cancer death in the United States and has a five-year survival rate of just 6 percent. In its mission to advance pancreatic cancer research and improve patient outcomes, the Pancreatic Cancer Action Network has collaborated with the AACR to promote and support outstanding research focused on conquering this deadly disease. The goals of the grants program are to build a robust pancreatic cancer research community; to encourage collaboration, information-sharing and innovation; and to expedite scientific and medical breakthroughs for patient benefit.

“We are thrilled to be able to expand our research portfolio this year to include the two inaugural RAN grants and to award such outstanding research projects as we work toward the Pancreatic Cancer Action Network’s goal to double the survival rate of pancreatic cancer by 2020,” said Lynn Matrisian, Ph.D., vice president of scientific and medical affairs at the Pancreatic Cancer Action Network and newly inaugurated Fellow of the AACR. “Since 2003, the organization has created a robust community of pancreatic cancer researchers and we look forward to integrating these new researchers into our team.”

The 2013 Pancreatic Cancer Action Network-AACR Inaugural Research Acceleration Network Grants are three-year grants totaling $1 million each. These grants offer strategic funding and project management services to a high-priority project already under way within the pancreatic cancer research community. This year’s recipients are:

Michael G. Goggins, M.D., Johns Hopkins University, Baltimore, Md.;
Marcia Irene Canto, M.D., Johns Hopkins University; and
Anil K. Rustgi, M.D., University of Pennsylvania, Philadelphia,
“CAPS Multicenter Trial: Imaging and Markers for Pancreatic Cancer Screening,”
Supported in memory of Skip Viragh

Robert H. Vonderheide, M.D., D.Phil., University of Pennsylvania and
Dafna Bar-Sagi, Ph.D., New York University, New York, N.Y.
“Accelerating Development of CD40 Therapy for Pancreatic Cancer,”
Supported by Tempur-Pedic in memory of Tim Miller

The 2013 Pancreatic Cancer Action Network-AACR Pathway to Leadership Grants are five-year grants totaling $600,000 each. These grants are designed to support the future leadership of pancreatic cancer research by funding outstanding early-career investigators beginning their postdoctoral, mentored research positions and continuing through a successful transition to independence. This year’s recipients are:

Costas A. Lyssiotis, Ph.D., Beth Israel Deaconess Medical Center, Boston, Mass.,
“Exploration and Targeting of Metabolic Dependencies in Pancreatic Cancer”

Yuliya Pylayeva-Gupta, Ph.D., New York University,
“Immunomodulatory Mechanisms in Kras-driven Pancreatic Cancer and Metastasis”

The 2013 Pancreatic Cancer Action Network-AACR Innovative Grants are intended to promote the development and study of novel ideas and approaches in basic, translational, clinical or epidemiological research that have direct application and relevance to pancreatic cancer. These two-year grants provide $200,000 over the grant term. This year’s recipients are:

Yves Boucher, Ph.D., Massachusetts General Hospital, Boston,
“Targeting Desmoplasia in Pancreatic Cancer to Improve Drug Efficacy,”
Supported by the Sobrato Family in memory of Abby Sobrato

M. Celeste Simon, Ph.D., University of Pennsylvania,
“Role of Hif1a in Inflammation, Tissue Repair and Cancer of the Pancreas”

Timothy Cragin Wang, M.D., Columbia University, New York, N.Y.,
“Dclk1 in Pancreatic Tumorigenesis”

Valerie M. Weaver, Ph.D., University of California, San Francisco,
“Interplay Between Tension and Inflammation in Pancreatic Tumor Progression,”
Supported by the Blum-Kovler Foundation

The 2013 Pancreatic Cancer Action Network-AACR Career Development Awards are two-year grants of $200,000 that are designed to attract and support early-career scientists as they conduct pancreatic cancer research and establish successful career paths in the field. This year’s recipients are:

Eric R. Lutz, Ph.D., Johns Hopkins University,
“Exploiting the Cancer Mutome for Personalized Tumor Immunotherapy”

Andrew D. Rhim, M.D., University of Pennsylvania,
“Using Human Circulating Pancreas Cells as a Biomarker for Early PDAC”

Pankaj Kumar Singh, Ph.D., University of Nebraska, Omaha,
“Targeting a Novel Metabolic Chemoresistance Mechanism in Pancreatic Cancer”

Daolin Tang, M.D., Ph.D., University of Pittsburgh, Pa.,
“Role of HMGB1 in Pancreatic Cancer Initiation and Progression”

Monte M. Winslow, Ph.D., Stanford University, Calif.,
“Molecular Dissection of Hmga2 Function During Pancreatic Cancer Progression,”
Supported in memory of Skip Viragh

The 2013 Pancreatic Cancer Action Network-AACR Fellowship is a one-year grant of $45,000 designed to support a postdoctoral investigator’s work in pancreatic cancer research. This year’s recipient is:

Andrew J. Aguirre, M.D., Ph.D., Dana-Farber Cancer Institute, Boston, Mass.,
“Validation of Novel KRAS Synthetic Lethal Targets in Pancreatic Cancer,”
Supported by Cynthia Stroum in memory of Samuel Stroum

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Media Contacts:

Lauren Riley
American Association for Cancer Research
(215) 446-7155
lauren.riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Jennifer Reeves Rosen
Pancreatic Cancer Action Network
jrosen@pancan.org
(310) 706-3362
In Washington, D.C.,
April 7-10, 2013:
(310) 460-8901

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

About the Pancreatic Cancer Action Network
The Pancreatic Cancer Action Network is the national organization creating hope in a comprehensive way through research, patient support, community outreach and advocacy for a cure. The organization is leading the way to increase the survival rate for people diagnosed with this devastating disease through a bold initiative—The Vision of Progress: Double the Pancreatic Cancer Survival Rate by 2020. Together, we can know, fight and end pancreatic cancer by intensifying our efforts to heighten awareness, raise funds for comprehensive private research, and advocate for dedicated federal research to advance early diagnostics, better treatments and increase chances of survival.

Meet these grant recipients and learn more about their funded projects.

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High Calcium Intake Associated With Reduced Colorectal Adenoma Risk in Certain Individuals

registration@aacr.org () — Wed, 10 Apr 2013 12:00:00 GMT

Prior studies associating calcium intake and colorectal adenoma risk have been inconsistent.
Variations in two specific genes were shown to modify the association.
Genetic tests may help determine which patients would benefit from higher calcium intake.

WASHINGTON, D.C. — Researchers have identified a potential explanation for inconsistent results from prior research about the association between calcium intake and risk for colorectal adenomas, which are precursors to colorectal cancers. The findings may help identify patients who would benefit from higher calcium intake or calcium supplementation, according to the researcher who presented the data at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

Previous studies suggested that a high intake of calcium was associated with a reduced risk for colorectal adenomas and cancer, but data from the Women’s Health Initiative did not support the benefit for colorectal cancer after seven years of follow-up, according to Xiangzhu Zhu, M.D., M.P.H., staff scientist in the Division of Epidemiology in the Department of Medicine at Vanderbilt-Ingram Cancer Center and Vanderbilt University School of Medicine in Nashville, Tenn.

Zhu and colleagues conducted a two-phase study to investigate whether the associations between risk for colorectal adenoma and intake of calcium and magnesium, as well as the calcium/magnesium ratio, were modified by common changes in 14 genes involved in controlling the amounts of calcium and magnesium in the body.

They evaluated 1,818 cases and 3,992 controls from the Tennessee Colorectal Polyp Study, a colonoscopy-based case-control study conducted in Nashville. Patients with the highest calcium intake showed no reduction in their risk for colorectal adenoma if they had no changes in either of two of the 14 genes analyzed, the KCNJ1 and SLC12A1 genes, both of which were identified and replicated in the two-phase study and are essential in calcium reabsorption in the kidney.

Fifty-two percent of the study population carried genetic changes in at least one of the two genes, and 13 percent of the population carried genetic changes in both genes. The highest calcium intake — patients in the top 33 percent — was significantly related to a 39 percent reduction in adenoma risk for patients who carried a genetic change in one gene and a 69 percent reduction in adenoma risk among those who carried genetic changes in both genes, according to Zhu. In addition, the corresponding reduction in risk for advanced or multiple adenomas was 89 percent among those with genetic changes in both genes.

According to Zhu, based on these data, a person with genetic changes in any of the two genes will see an increased risk for adenoma if they consume less than about 1,000 mg of calcium a day, especially if they carry genetic changes in both genes. The risk will increase by more than 50 percent for an adenoma and by 120 percent for advanced or multiple adenomas. “These patients should increase their calcium intake to reduce the risks,” Zhu said.

“Our results may provide one possible explanation for the inconsistency in previous studies on calcium intake and colorectal abnormalities because calcium may primarily prevent colorectal cancer in the early stage and reduce risk only among those with genetic changes in calcium reabsorption, which involves KCNJ1 and SLC12A1,” Zhu said. “If confirmed in future studies, our findings will be critical for the development of new personalized prevention strategies for colorectal cancer.”

The study was funded by National Institutes of Health (National Center for Complementary and Alternative Medicine/Office of Dietary Supplements) Grant Number 5R01AT004660-04 (PI: Qi Dai). The project was conducted using resources collected from the Tennessee Colorectal Polyp Study, a project of the Vanderbilt Gastrointestinal Cancer Specialized Program of Research Excellence.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

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RNA Interference Drug Demonstrated Activity and Safety in Phase I Trial

registration@aacr.org () — Tue, 09 Apr 2013 12:00:00 GMT

RNA interference drugs silence specific genes.
Investigational drug silences the PLK1 gene involved in tumor growth.
Most patients tolerated the drug well; some showed therapeutic benefit.

WASHINGTON, D.C. — Early results from a phase I, first in-human study indicate that a potential new class of drugs, RNA interference (RNAi) drugs, can be safely administered in humans, according to a researcher who presented data on the safety and preliminary efficacy of TKM-080301 at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10. TKM-080301, also known as TKM-PLK1, is an RNAi drug being developed by Tekmira Pharmaceuticals Corporation.

“RNAi therapies are a unique approach to cancer treatment as they have the potential to ‘turn off’ the genes’ coding for proteins involved in cancer cell division,” said Ramesh K. Ramanathan, M.D., medical director of the Virginia G. Piper Cancer Center Clinical Trials Program at Scottsdale Healthcare and deputy director of the Clinical Translational Research Division of the Translational Genomics Research Institute (TGen) in Phoenix, Ariz. “Using a lipid nanoparticle, the RNAi drug can be delivered to a cancer cell to block the expression of specific proteins involved in tumor growth.”

TKM-080301 targets a specific gene called polo-like kinase 1 (PLK1), which codes for a protein involved in tumor cell growth. Prior research has shown that high levels of PLK1 are present in many types of cancer, including many of the more aggressive forms.

“Our preclinical results have shown that by decreasing PLK1 levels in cancer cells, we can stop tumor growth and kill the cancer cells,” Ramanathan said.

He and his colleagues have been enrolling patients with advanced solid tumors or lymphoma into the ongoing multicenter, open-label, dose-escalation study. Sequential cohorts of three to six patients have been assigned to escalating doses of TKM-080301 as a 30-minute intravenous infusion. To date, the researchers have assigned 23 patients to the drug at doses ranging from 0.15 mg/kg per week to 0.9 mg/kg per week.

The most common drug-related adverse events have been mild to moderate and include fever, chills, nausea, vomiting and fatigue. Dose-limiting toxicities were observed at the 0.9 mg/kg per-week dose. One patient with a history of asthma experienced shortness of breath and hypoxia; another patient had thrombocytopenia. The researchers subsequently reduced the maximum dose to 0.75 mg/kg per week.

Two patients have been assigned to TKM-080301 for more than six months and have shown no evidence of cumulative toxicity. One of these patients has stable disease and the other has a durable confirmed partial response.

“RNAi therapies, such as the one used in our study, have the potential to make a significant and broad impact on how we treat cancer because we have the ability to target virtually any protein involved in the disease,” Ramanathan said. “This approach has the potential to augment the currently available cancer treatments to improve outcomes for the patient.”

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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Engineered Antibody Demonstrated Safety, Efficacy in Wide Range of Advanced Tumors

registration@aacr.org () — Tue, 09 Apr 2013 12:00:00 GMT

The PD-L1 antibody MPDL3280A displayed antitumor activity across a range of cancer types, including lung, kidney, colon and stomach cancers.
MPDL3280A was well tolerated.
Phase I study results demonstrated no limiting toxicities.

WASHINGTON, D.C. — The engineered antibody MPDL3280A, which targets a protein called programmed death-ligand 1 (PD-L1), was safe and effective for several cancers, according to phase I study results presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“Our PD-L1 antibody was well tolerated, and there were no limiting toxicities,” said Michael S. Gordon, M.D., research director at Pinnacle Oncology Hematology in Scottsdale, Ariz. “It was active with antitumor activity across a broad range of cancers, and we have developed biomarker tools that we are testing, which may allow us to optimize patient selection for this novel therapy.”

PD-L1, a protein found on the surface of many cancer cells, impairs the immune system’s ability to fight cancer, according to Gordon.

“PD-L1 is essentially a plug, which inserts into an outlet (PD-1) on the surface of the immune T cells,” Gordon said. “As the T cells come close to the tumor, for example, they are engaged by PD-L1, which inserts into the outlet on the surface of the T cell. That starts a signal inside the T cell that blocks the T cell’s ability to kill the cancer cell.”

MPDL3280A, a human monoclonal antibody under development by Genentech, a member of the Roche Group, binds to PD-L1 and blocks this action.

Gordon and colleagues administered an escalating intravenous dose of MPDL3280A once every three weeks to 30 patients with a variety of locally advanced or metastatic solid tumors. They escalated the dose from 0.01 mg/kg to as high as 20 mg/kg. The data being presented are the preliminary data from the dose escalation cohorts of the ongoing phase I trial.

No dose-limiting toxicities or grade 4 adverse events have been reported. “We were able to escalate to the top dose without being limited by any serious side effects,” Gordon said.

“From a therapeutic standpoint, we were able to identify a number of patients with a broad range of diseases, including lung cancer, kidney cancer, colon cancer and stomach cancer, who responded to the treatment,” he said.

A second protein, called PD-L2, fits into the same T-cell “outlet” as PD-L1, according to Gordon. MPDL3280A is specific for PD-L1; it does not block PD-L2, which is expressed in noncancerous tissues including the lung, he added.

“One would anticipate, compared with drugs being developed to specifically block the T-cell outlet (PD-1) and, therefore, block the relationship between the outlet and both PD-L1 and PD-L2, that we might see less lung or pulmonary toxicity with MPDL3280A. But we need to conduct larger studies to confirm this.”

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

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Prevalence of Benign Disease Diagnosis After Lung Surgery Varied Widely by State

registration@aacr.org () — Tue, 09 Apr 2013 12:00:00 GMT

Prevalence of benign lung disease ranged from 1.2 percent in Vermont to 25 percent in Hawaii.
2.1 percent of patients with a benign diagnosis died in the hospital after surgery.
Benefits of lung cancer screening may differ widely by state.

WASHINGTON, D.C. — Benign disease diagnosis rates after surgery for suspected lung cancer varied widely by state, and the reasons for these variations could inform health policy and clinical guidelines for lung cancer screening, according to a researcher who presented the data at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“Given the results of the National Lung Screening Trial (NLST), which demonstrated that low-dose computed tomography (CT) reduces lung cancer mortality, and the support for screening healthy, high-risk individuals with low-dose CT by clinical and patient advocacy groups, we will likely see screening for lung cancer in our near future,” said Stephen A. Deppen, a doctoral candidate in epidemiology and database analyst at Vanderbilt University in Nashville, Tenn.

Data from NLST revealed that low-dose CT screening led to a 20 percent reduction in lung cancer-related mortality compared with chest X-ray; however, 96 percent of the positive screening results were false positives and 24 percent of follow-up lung resections were negative for lung cancer.

“It was not known whether the prevalence of benign disease diagnosis after lung resection for suspected lung cancer is uniform across the United States,” said Deppen. “If prevalence differs by state or region of the country, then a national lung cancer screening program may have varying results.”

He and his colleagues, therefore, set out to determine the prevalence of benign disease diagnosis rates by state.

Using the Medicare Provider Analysis and Review (MedPAR) Hospital National Limited Data Set from 2009, Deppen and colleagues evaluated medical data from 25,362 patients who underwent lung surgery for known or suspected lung cancer.

They found that 2,312 patients (9.1 percent) had a benign disease diagnosis after surgery. About 2.3 percent of all patients died in the hospital after the procedure. For those who were found not to have lung cancer, the mortality rate was 2.1 percent.

In addition, there was a wide variation among states in the prevalence of benign disease diagnosis, from 1.2 percent in Vermont to 25 percent in Hawaii.

“States with a higher rate of false positives and higher benign disease prevalence may observe poorer performance of a screening program for lung cancer,” Deppen said. “The benefit of screening for lung cancer is finding early-stage disease and reducing mortality from lung cancer. Lung surgery is major surgery and has a much higher risk for death and complications compared with diagnostic operations for other cancers, such as breast and prostate cancer. So, more surgeries for benign disease will result in more deaths and harm from the diagnostic process and will reduce the benefit that was observed in the original NLST.”

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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Cohort Study Indicates That Selenium May Be Protective Against Advanced Prostate Cancer

registration@aacr.org () — Tue, 09 Apr 2013 12:00:00 GMT

Higher toenail selenium levels were associated with a reduced risk for advanced prostate cancer.
Toenail selenium levels reflect long-term selenium intake.
Further studies in low-selenium populations are required.

WASHINGTON, D.C. — A greater level of toenail selenium was associated with a significant decrease in the risk for advanced prostate cancer, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“This could mean, based on our data and based on data from other studies, that selenium is a modifiable risk factor of advanced, clinically relevant prostate cancer,” said Milan S. Geybels, M.Sc., a doctoral candidate in cancer epidemiology at Maastricht University, in Maastricht, the Netherlands.

The Netherlands Cohort Study on diet and cancer is a prospective cohort study that includes 58,279 men who were aged 55 to 69 years at entry in September 1986. Geybels and colleagues analyzed data from 898 men who were diagnosed with advanced prostate cancer during 17.3 years of follow-up of the cohort.

According to Geybels, previous studies investigating the association between selenium levels and prostate cancer have yielded varying results. One large clinical trial showed that selenium supplementation had no protective effect, while several prospective, observational studies indicated that higher levels of selenium were associated with a reduced prostate cancer risk, especially for advanced prostate cancer.

“Our study is interesting because we specifically investigated men with advanced prostate cancer, a type of prostate cancer associated with a poorer prognosis,” Geybels said. “Also, while most of the prior research, including the large clinical trial, involved men with moderate-to-high selenium levels, men in The Netherlands Cohort Study have selenium levels that range from low to moderate. This is important because low selenium is expected to be related to a higher disease risk.”

He and his colleagues chose toenail selenium as the study biomarker because it reflects long-term exposure, as opposed to blood, which is best for monitoring recent selenium exposures.

The data revealed that greater levels of toenail selenium were associated with a substantially reduced risk for advanced prostate cancer. Men with the highest toenail selenium levels had a more than 60 percent lower risk for advanced prostate cancer compared with men with the lowest toenail selenium levels.

“Our findings need to be replicated in further prospective studies, with an extended follow-up for the assessment of incident advanced prostate cancer, and with a wide range of toenail selenium that includes low selenium levels,” Geybels said. “If our results can be confirmed, a prevention trial of selenium and prostate cancer in a low-selenium population may be justified.”

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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Exposure to Air Pollution During Pregnancy Linked to Increased Incidence of Specific Pediatric Cancers

registration@aacr.org () — Tue, 09 Apr 2013 12:00:00 GMT

Exposure during pregnancy was associated with an increased incidence of three cancers.
The highest increases were found for retinoblastoma and germ cell tumors.
Findings require replication in other large studies.

WASHINGTON, D.C. — Increased exposure to traffic-related air pollution during pregnancy was associated with a higher incidence of acute lymphoblastic leukemia and two rare childhood cancers, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“The main reason for undertaking this study was that we know much more about the causes of adult cancers than we do of the causes of childhood cancers,” said Julia Heck, Ph.D., M.P.H., assistant researcher in the Department of Epidemiology at the University of California, Los Angeles School of Public Health. “We studied pregnancy exposures because the fetus is likely to be more vulnerable to environmental factors during that time, and we also know that certain childhood cancers originate in utero.”

Heck and her colleagues identified 3,590 children from the California Cancer Registry born between 1998 and 2007 who could be linked to a California birth certificate. Children were five years of age or younger at diagnosis. Researchers selected controls at random from 80,224 children listed on California birth rolls. They used the California Line Source Dispersion Modeling Version 4 (CALINE4) to generate estimates of local traffic exposure at the mother’s home during each trimester of pregnancy and during the child’s first year of life. Estimates were based on local traffic emissions of gasoline vehicles and diesel trucks within a 1,500-meter radius buffer and included traffic volumes, roadway geometry, vehicle emission rates and meteorology.

Each interquartile range increase in exposure to traffic-related pollution was associated with an increased risk for developing acute lymphoblastic leukemia (4 percent), retinoblastoma (14 percent for all cases of the disease; 11 percent for retinoblastoma affecting just one eye and 19 percent for retinoblastoma affecting both eyes) and germ cell tumors (17 percent).

Because CALINE4 estimates were highly correlated across trimesters and during the first year of life, the researchers were not able to determine the most important period in terms of exposure.

“This is the first study that’s ever been reported on air pollution as it relates to rarer pediatric cancers, so it needs to be replicated in other states or in other countries,” Heck said. “It would be interesting to determine if there are specific pollutants like benzene or polycyclic aromatic hydrocarbons that are driving these associations.”

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

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New Approach Evaluates Effect of Physical Activity on Estrogen Metabolism in Postmenopausal Women

registration@aacr.org () — Tue, 09 Apr 2013 12:00:00 GMT

Study used direct measures of physical activity and comprehensive analysis of urinary estrogen levels.
Increased physical activity was related to lower urinary levels of estrogens and four estrogen metabolites.
These data have implications for understanding the link between physical activity and breast cancer risk.

WASHINGTON, D.C. — Researchers have generated new insights into the ways in which physical activity affects how much estrogen is broken down and secreted in the urine of postmenopausal women. These findings enhance understanding of the potential biological mechanisms linking increased physical activity and decreased risk for breast cancer in postmenopausal women, according to the scientist who presented the data at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

Previous studies have suggested that increased physical activity may reduce the risk for breast cancer among postmenopausal women, and that this might be a result of physical activity lowering endogenous estrogen levels, according to Cher Dallal, Ph.D., a National Cancer Institute (NCI) cancer prevention fellow. However, few studies have evaluated the influence of physical activity on the breakdown of estrogens in postmenopausal women. This breakdown process, called estrogen metabolism, results in a variety of molecules known as metabolites.

“This is the first study to consider the relationship between accelerometer-measured activity and a panel of estrogen metabolites measured in urine,” said Dallal. “We hoped by using direct measures to examine this relationship that we could improve our knowledge of how these factors may influence cancer risk among postmenopausal women.”

Dallal and colleagues studied 540 healthy, postmenopausal women who were enrolled in the NCI Polish Breast Cancer Study, conducted from 2000 to 2003. None of the women were taking menopausal hormone therapy. The investigators measured physical activity by accelerometer, which is a small device that women wore on their waists during waking hours for seven days. According to Dallal, accelerometers provide objective readings of physical activity compared with participants’ self-reports, which have been the predominant measure in previous studies.

Women also provided a 12-hour urine sample. The researchers tested the samples for estradiol and estrone, two “parent” estrogens, plus 13 different estrogen metabolites using a new assay developed by the NCI. According to Dallal, this novel assay can detect multiple urinary estrogens, compared with those used in previous studies that only measured one or two metabolites individually.

The researchers found that increased physical activity was associated with lower levels of parent estrogens. In addition, higher levels of physical activity were associated with lower levels of four specific estrogen metabolites. Dallal cautions, however, that further research on estrogen metabolism will be needed to understand how these metabolites play a role in mediating breast cancer risk.

“By using these new tools to study the relationship between activity and estrogen metabolism, we hope to get closer to uncovering the combination of parent estrogens, metabolites and metabolism pathways that are related to a lower-risk profile of breast cancer,” said Dallal.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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AACR Releases Policy Guidance on Tobacco and Cancer Clinical Trials

registration@aacr.org () — Tue, 09 Apr 2013 12:00:00 GMT

Statement calls for greater efforts in smoking cessation.
Tobacco use should be evaluated as a confounding factor in clinical trials.
Surveys show tobacco use is often not measured.

WASHINGTON, D.C. — An American Association for Cancer Research (AACR) statement calls on the oncology community to provide evidence-based tobacco cessation treatment for all cancer and cancer-screening patients and to evaluate tobacco as a confounding factor in cancer clinical trial outcomes. The statement was published this morning in Clinical Cancer Research, a journal of the AACR.

Tobacco use is the single largest preventable cause of cancer in the United States, and smoking cessation treatment has long been regarded as a key cancer prevention strategy. However, research has shown that such treatment is often lacking in oncology settings.

A survey of National Cancer Institute (NCI)-designated cancer centers indicated that only 38 percent of the responding centers record smoking as a vital sign, and less than 50 percent have dedicated tobacco cessation personnel. These findings are unfortunate, as evidence shows that continued tobacco use during and after cancer treatment leads to more adverse side effects, poorer treatment outcomes and higher overall mortality from all causes.

“We have made great strides in treating cancer, and people are living for decades after a cancer diagnosis,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “If, however, we do not address patient’s tobacco use, then we leave them at risk for failing cancer treatment, developing new malignancies, and premature death from non-cancer causes such as cardiovascular disease. With this statement, we call on all oncology professionals to take responsibility for identifying tobacco users at every visit and ensuring that these patients get the treatment and support they need.”

In addition to compromising their treatment and overall health, continued smoking by patients with cancer can complicate the interpretation of clinical trial outcomes. “Tobacco, like other drugs, has adverse side effects and can interfere with the effectiveness of cancer treatments,” said Roy Herbst, M.D. Ph.D., chair of the AACR Subcommittee on Tobacco and Cancer and chief of medical oncology at Yale Comprehensive Cancer Center in New Haven, Conn. “We have to get to a point in clinical trials where we factor a patient’s tobacco use into how we evaluate patient outcomes, just like we do with other drugs or comorbidities. Right now, the field is not doing that with any regularity.”

A recent evaluation of 155 NCI Cooperative Group trials showed that as few as 29 percent of registered trials assessed any form of tobacco use in patients at enrollment, and less than 5 percent of registered trials assessed tobacco use during follow-up. In addition, a newly published large survey of oncologists demonstrates that while 90 percent believe that tobacco use affects cancer outcome and that tobacco cessation should be a standard part of cancer care, only 40 percent regularly provide assistance to stop using tobacco.

In the statement issued today, the AACR calls for universal tobacco use assessment and documentation at every patient visit in all clinical cancer settings. “Whether they are being treated in a community oncology setting or as part of a cancer clinical trial, we must help patients end their tobacco addiction, but we can’t do that unless the patient has been identified as a tobacco user,” said Benjamin Toll, Ph.D., program director of the Smoking Cessation Service at Smilow Cancer Hospital at Yale-New Haven Hospital and chair of the writing committee charged with developing the AACR policy statement.

AACR’s policy statement was developed by the Tobacco and Cancer Subcommittee of the AACR Science Policy and Government Affairs Committee and follows a 2010 policy statement that addressed a broader spectrum of tobacco control and research issues.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
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AACR Inaugurates New Leadership at 2013 Annual Meeting

registration@aacr.org () — Tue, 09 Apr 2013 12:00:00 GMT

Charles L. Sawyers, M.D., is the new AACR president
Frank McCormick, Ph.D., F.R.S., D.Sc. (hon.), now serves as past-president
Carlos L. Arteaga, M.D. is inducted as president-elect

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) announced its new leadership today as Charles L. Sawyers, M.D., became president of the organization for 2013-2014. He was inaugurated during the Annual Business Meeting, held in Washington, D.C., April 6-10.

“The AACR is an extraordinary organization and I’m privileged to be able to serve as president,” said Sawyers. “This is an exciting time in cancer research, as we see so many promising therapies emerging from our work. But it is also a time of financial strain, and we must be sure that Washington understands that it is imperative that we continue to invest in medical research. As president of the AACR, I will work with the organization to make sure that this message is heard, because it is imperative that the AACR and its members are in the strongest position to continue to have a positive effect on the lives of those touched by cancer.”

Sawyers is chair of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center and a Howard Hughes Medical Institute investigator. He is also a professor in the Cell and Developmental Biology Program and Department of Medicine at the Joan and Sanford I. Weill Graduate School of Medical Sciences of Cornell University in New York, N.Y.

Sawyers conducts research to investigate the signaling pathways that drive the growth of cancer cells, particularly in the context of drug resistance, with an eye toward designing new treatment options. His laboratory is currently exploring the molecular basis of prostate cancer and mechanisms of resistance to hormone therapy. This work is focused on the role of the androgen receptor in disease progression, even when tumors progress to the hormone-refractory stage. Additional projects include deciphering mechanisms of resistance to enzalutamide (formerly MDV3100), a novel antiandrogen discovered by his group that was approved by the U.S. Food and Drug Administration in 2012. His lab is also dissecting androgen-receptor function using RNA-interference screens and examining crosstalk between the androgen receptor and other common molecular lesions in human prostate cancer such as PTEN loss and TMPRSS2-ERG gene fusions.

He shared the 2009 Lasker~DeBakey Clinical Medical Research Award for earlier work leading to the development of the ABL kinase inhibitor imatinib (Gleevec) for patients with chronic myeloid leukemia, and the second-generation ABL inhibitor dasatinib (Sprycel) to overcome imatinib resistance.

Sawyers has received numerous other accolades, including the AACR-Richard and Hinda Rosenthal Foundation Award, the Dorothy P. Landon-AACR Prize for Translational Cancer Research, the Doris Duke Distinguished Clinical Scientist Award, the American Society of Clinical Oncology David A. Karnofsky Award and, most recently, the Breakthrough Prize in Life Sciences and the 2013 American Cancer Society/Society of Surgical Oncology Basic Science Lecture.

Sawyers is a co-leader of the Stand Up To Cancer-Prostate Cancer Foundation Dream Team “Precision Therapy of Advanced Prostate Cancer.” The AACR is the scientific partner for Stand Up To Cancer.

Sawyers has served the AACR in numerous capacities. He is a scientific editor for Cancer Discovery, the associate editor of Clinical Cancer Research and was an associate editor for Cancer Research.

In addition, he was a keynote speaker and scientific committee co-chairperson for the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; co-chairperson of the AACR’s special conferences, Targeting the PI3 Kinase Pathway in Cancer and Emerging Concepts in Oncology; and chairperson of the AACR’s educational workshop Molecular Biology in Clinical Oncology. Sawyers has served previously as a member of the AACR Board of Directors, the Nominating Committee and the AACR Award for Lifetime Achievement in Cancer Research Committee.

Sawyers is a past president of the American Society of Clinical Investigation, serves on President Obama’s National Cancer Advisory Board and is a member of the Institute of Medicine and the National Academy of Sciences.

Sawyers received his medical degree from the Johns Hopkins School of Medicine in 1985. He completed his residency training at the University of California, San Francisco (UCSF), and then joined the fellowship program of the Division of Hematology-Oncology at the University of California, Los Angeles (UCLA). In 1993, Sawyers became an assistant professor at UCLA, and three years later was appointed associate chief of basic research and director of the Hematopoietic Malignancies and Bone Marrow Transplant Program. In 2002, he was named a Howard Hughes Medical Institute investigator and joined Memorial Sloan-Kettering Cancer Center in 2006 to chair the Human Oncology and Pathogenesis Program.

Frank McCormick, Ph.D., F.R.S., D.Sc. (hon.), served with distinction as the AACR president for the 2012-2013 term and will now fulfill the role of past president for 2013-2014. McCormick is the director of the UCSF Helen Diller Family Comprehensive Cancer Center. He holds the E. Dixon Heise distinguished professorship in oncology and the David A. Wood distinguished professorship of tumor biology and cancer research at UCSF. Additionally, he is the associate dean of the UCSF School of Medicine and a distinguished professor in residence in the Department of Microbiology and Immunology, as well as in the Department of Biochemistry and Biophysics.

McCormick is a pioneer in cancer research. He has studied the molecular basis of cancer and how genes, when mutated or expressed at high levels, help turn normal cells into oncogenes. In 1992, he founded the biotech company Onyx Pharmaceuticals and developed Nexavar, which is used to treat advanced renal cell carcinoma and hepatocellular carcinoma. His current research interests center on the Ras pathway and new ways of targeting this pathway for cancer therapy.

Among his service to the AACR, McCormick served as program chairperson for the 2010 Annual Meeting and as a member of the board of directors and co-chair of the Annual Meeting Program Committee. He chairs the Task Force on Regulatory Science and Policy and previously chaired the Award for Lifetime Achievement in Cancer Research and the Team Science Award Committees. He is a member of the Special Conferences Committee and participated in the Scientific Review and Program Committees for the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics meeting. McCormick is a scientific editor of Cancer Discovery and was a senior editor of Molecular Cancer Research.

He was the recipient of the 2002 AACR G.H.A. Clowes Memorial Award for outstanding accomplishments in basic cancer research and was inaugurated into the first class of Fellows of the AACR Academy at the AACR Annual Meeting 2013.

McCormick is a member of the Institute of Medicine of the National Academies and a fellow of The Royal Society, United Kingdom. He was awarded an honorary Doctor of Science degree from the University of Birmingham, United Kingdom.

McCormick has also received the Science of Oncology Award from the American Society of Clinical Oncology, the Bristol-Myers Squibb Unrestricted Cancer Research Grant, the Novartis Drew Award in Biomedical Research and the Shubitz Award from the University of Chicago Cancer Research Center. He has served as a board member and advisor for numerous cancer research organizations, including the Association of American Cancer Institutes, the Melanoma Therapeutics Foundation, the Canary Foundation, the Alliance for Cancer Gene Therapy and Friends of Cancer Research.

McCormick received his bachelor’s degree in biochemistry from the University of Birmingham and his doctorate in biochemistry from the University of Cambridge. He was a postdoctoral fellow at the State University of New York at Stony Brook and at the Imperial Cancer Research Fund in London.

Carlos L. Arteaga, M.D., is AACR president-elect for 2013-2014 and will assume the presidency in April 2014. Arteaga is a professor of medicine and cancer biology at Vanderbilt University School of Medicine, in Nashville, Tenn., where he holds the Donna S. Hall chair in breast cancer research. He also serves as associate director for clinical research and director of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center.

Arteaga’s research interests include oncogene signaling and molecular therapeutics in breast cancer, with an emphasis on targeted therapies, mechanisms of drug resistance, translational research and investigator-initiated clinical trials. Early in his career, he was the first to report the role of IGF-I receptors and TGF beta in breast cancer progression and, as such, their potential as therapeutic targets. More recent work has focused on the role of presurgical and neoadjuvant trials to discover molecular biomarkers that inform patient selection in clinical trials and/or for the discovery of mechanisms of drug resistance in breast cancer. In studies focused on hormone receptor-positive breast cancer, he showed the role of aberrant activation of the PI3 kinase pathway in promoting escape from antiestrogens and the ability of inhibitors of HER2 and PI3 kinase to reverse resistance to antiestrogen therapy in human breast cancer. His work has significant implications for novel clinical trials in patients with breast cancer.

Arteaga’s involvement in the AACR spans more than a decade. He was a member of the Board of Directors (2004-2007); chair of the AACR Special Conferences Committee (2002-2008); member of the Annual Meeting Program Committee (2012 and 2013); co-chairperson of the special conference Molecularly Targeted Therapies: Mechanisms of Resistance (2012); member of the Clinical and Translational Cancer Research Grants Scientific Review Committee (2012); member of the AACR Outstanding Investigator Award for Breast Cancer Research Selection Committee (2011); co-chairperson of the AACR-Japanese Cancer Association joint conference; co-chair of the AACR special conference Advances in Breast Cancer Research (2003, 2005, 2007, 2009 and 2013); and an editorial board member of the AACR’s journal Molecular Cancer Therapeutics (2002-2012).

Arteaga was an editorial board member for Clinical Cancer Research from 2001 to 2004 and is currently deputy editor. He has served as co-chair of the annual CTRC–AACR San Antonio Breast Cancer Symposium since 2009 and is a principal investigator on the Stand Up To Cancer Dream Team, “Targeting the PI3K Pathway in Women’s Cancers.”

He has received many honors and awards, including the AACR-Richard and Hinda Rosenthal Award; the American Cancer Society Clinical Research Professor Award; the Gianni Bonadonna Award from the American Society of Clinical Oncology; the Brinker Award for Scientific Distinction from the Susan G. Komen for the Cure Breast Cancer Foundation; and the Clinical Investigator Award from the U.S. Department of Veteran Affairs. Additionally, he is a member of the Association of American Physicians, the American Society for Clinical Investigation and Susan G. Komen’s Scientific Advisory Board.

Arteaga received his medical degree in 1980 from the Facultad de Ciencias Médicas at the Universidad de Guayaquil in Ecuador. Following an internal medicine residency at Emory University in Atlanta, Ga., Arteaga completed a fellowship in medical oncology at The University of Texas Health Science Center at San Antonio. He joined the faculty at Vanderbilt University in 1989.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Novel AKT Pathway Inhibitor, ARQ 092, Demonstrated Safety, Effective Target Inhibition

registration@aacr.org () — Mon, 08 Apr 2013 12:00:00 GMT

ARQ 092 was active and had a manageable safety profile.
Hyperglycemia in patients indicated effective AKT pathway inhibition.
Hyperglycemia occurred prior to dose-limiting skin toxicity and could be treated.

WASHINGTON, D.C. — Researchers have confirmed that the novel oral agent ARQ 092 inhibits the AKT pathway and has a manageable safety profile in patients with a variety of advanced solid tumors, according to phase I data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“AKT is a signal transduction pathway crucially involved in the growth, survival and metabolism of cancer cells,” said Mansoor N. Saleh, M.D., professor of medicine at the University of Alabama Comprehensive Cancer Center in Birmingham and director of research at Georgia Cancer Specialists in Atlanta. “Many of the signaling pathways disrupted by commonly seen cancer-causing mutations merge into the AKT pathway. In addition, the AKT pathway is often amplified and mutated in patients who relapse following initial therapy.

“This means that the AKT pathway is a potential treatment target for numerous cancer types, either at diagnosis or when they become resistant to initial therapies.”

Saleh and his colleagues tested the safety and activity of ARQ 092 in patients with a broad range of advanced or metastatic solid tumors, including colorectal, endometrial and neuroendocrine cancers. They assigned patients in the first cohort to a dose of 10 mg every other day and enrolled subsequent patients into cohorts of three to six patients who were assigned to a dose escalation schedule with the drug.

“This class of agents has two common toxicities, namely skin toxicity and hyperglycemia, a rise in blood sugar levels,” Saleh said. “Based on data presented with other AKT inhibitors, skin toxicity has been the dose-limiting side effect and often resulted in drug discontinuation.”

To date, Saleh and colleagues have observed no dose-limiting skin toxicity. In addition, they have observed that with ARQ 092, blood sugar levels rise before patients experience skin toxicity, and they have been able to treat the hyperglycemia, thus allowing the patients to continue on the experimental drug.

“When we see hyperglycemia, we know that the drug is active in patients,” Saleh said. “We can ameliorate the high blood sugar, potentially allowing us to achieve drug levels that will be therapeutically active.”

Currently, the maximum tolerated dose has not been reached in this ongoing trial, but Saleh and colleagues have confirmed that the 80-mg dose once a day is not well tolerated. Seven patients have remained stable on the drug for more than four months. Four patients with advanced and refractory solid tumors have had stable disease for longer than six months, according to Saleh.

Once the maximum tolerated dose is identified, Saleh and colleagues plan to test the drug for efficacy.

“We will also explore the drug activity in patients with a high level of AKT in the tumor to identify the patient populations that can robustly benefit from our treatment,” he said.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Patients With BRCA1 Mutations, but Not BRCA2 Mutations, Had Poorer Prognosis Compared With Noncarriers

registration@aacr.org () — Mon, 08 Apr 2013 12:00:00 GMT

Patients with BRCA1 mutations were 1.2 times more likely to die from breast cancer.
There was no significant difference in survival for those with BRCA2 mutations.
ER-positive tumors were less prevalent among those with BRCA1 mutations.

WASHINGTON, D.C. — Patients with breast cancer who had a BRCA1 mutation had significantly worse overall and recurrence-free survival rates compared with patients without BRCA mutations, but no evidence for a difference in survival was found between patients with BRCA2 mutations and those without a BRCA mutation, according to data from a large Dutch study presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

Previous studies investigating survival differences between women with BRCA1 or BRCA2 mutations and those without a BRCA mutation, or noncarriers, have been inconsistent, according to Marjanka M. K. Schmidt, Ph.D., a group leader in the Experimental Therapy Division of the Netherlands Cancer Institute in Amsterdam. “We have analyzed data from one of the largest, least biased, BRCA1/2-genotyped breast cancer cohorts,” she said.

Schmidt and colleagues evaluated BRCA status and survival in 5,518 patients who had been diagnosed with breast cancer before the age of 50 and had been treated at any one of 10 cancer clinics in the Netherlands. They found that 3.6 percent of the patients had a BRCA1 mutation and 1.2 percent had a BRCA2 mutation.

Researchers tested patients’ samples for 78 different inherited BRCA1 or BRCA2 mutations and linked these to long-term outcome during a mean follow-up of 11.3 years. The proportion of ER-positive tumors was similar between noncarriers’ tumors (86 percent) and tumors from patients with a BRCA2 mutation (81 percent) but was low among tumors from patients with BRCA1 mutations (29 percent).

The data revealed that women with a BRCA1 mutation were 1.5 times more likely to have a breast cancer recurrence and were 1.2 times more likely to die from breast cancer compared with noncarriers. There was no evidence for worse survival among patients with BRCA2 mutations compared with noncarriers.

In preliminary analyses, the effect of BRCA1 on survival remained after the researchers adjusted for tumor characteristics. “However, in our review, we also found that the effects were attenuated when tumor characteristics were adjusted for,” Schmidt said. “So part of the worse survival in BRCA1 mutation carriers is likely explained by tumor characteristics and part by the mutation itself.”

The differences in survival between BRCA1 mutation carriers and noncarriers might indicate that treatment should depend, in part, on which mutation a woman has, according to Schmidt.

“Currently, patients are treated on the basis of their tumor characteristics, not on their BRCA status, aside from prophylactic measures and, for example, PARP inhibitors in clinical trials,” she said. “If we could show that BRCA status, independent of tumor characteristics, is predictive of prognosis, this could be taken into account in prediction models and could facilitate treatment decisions.”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Some Melanoma Survivors Still Use Tanning Beds, Skip Sunscreen

registration@aacr.org () — Mon, 08 Apr 2013 12:00:00 GMT

Most melanoma survivors engage in more sun protection practices than the general public.
More than 2 percent of melanoma survivors use tanning beds.
Twenty-seven percent of melanoma survivors never wear sunscreen.

WASHINGTON, D.C. — Although most survivors of melanoma take precautions to protect their skin from the sun and further occurrences of cancer, data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10, revealed that more than a quarter do not use sunscreen when outside for more than an hour, and more than 2 percent still use tanning beds.

“We know that melanoma is a malignancy prevalent in our population, and we know that for many people with melanoma, sun exposure is a major risk factor for recurrence and sun protection may reduce their chances of getting melanoma again,” said Anees B. Chagpar, M.D., M.P.H., associate professor of surgery at Yale School of Medicine, in New Haven, Conn., and director of the Breast Center at Smilow Cancer Hospital at Yale-New Haven. “Although we found that melanoma survivors did better than the general public at protecting their skin from the sun, we also found that more than a quarter of melanoma survivors never wear sunscreen. That blew my mind.”

Chagpar and colleagues evaluated data from the 2010 National Health Interview Survey, an annual, cross-sectional survey of the civilian, noninstitutionalized population of the United States that asks questions on a wide range of health topics. They focused on data collected on self-reported history of melanoma, sun protection practices and indoor tanning.

Of 27,120 adults, 171 had a prior history of melanoma. Researchers found that compared with those individuals who reported no history of melanoma, survivors were more likely to stay in the shade (15.6 percent versus 10.5 percent of the general population) and wear a baseball cap/visor (31.3 percent versus 18.4 percent), wide-brimmed hat (20.5 percent versus 6.1 percent) and/or long-sleeved shirt (12 percent versus 5.2 percent) when outside on a warm, sunny day for more than an hour. They were also more likely to always wear sunscreen (32 percent versus 17.2 percent).

However, 15.4 percent of melanoma survivors still reported rarely or never staying in the shade, 27.3 percent reported never wearing sunscreen when going outside on a warm, sunny day for more than an hour (compared with 35.4 percent of the general population), and 2.1 percent reported using a tanning bed during the previous year (compared with 5.5 percent of the general population).

“We now know that a significant proportion of melanoma survivors still could be doing better. This study speaks to what we could do to educate melanoma survivors on how to prevent recurrence,” Chagpar said.

In addition, she recommended researchers use the data to educate the general population, as the results revealed that only 17.2 percent of Americans will always use sunscreen and 5.5 percent still use tanning beds.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Katie Couric Honored With 2013 AACR Award for Distinguished Public Service

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) presented Katie Couric with the 2013 AACR Award for Distinguished Public Service in recognition of her extraordinary contributions as an advocate for cancer research, early detection and prevention, as well as her visionary leadership and commitment to the conquest of cancer, particularly colon cancer.

The AACR Award for Distinguished Public Service was presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10, during the opening ceremony on Sunday, April 7, at 8:30 a.m. ET in Halls D-E in the Walter E. Washington Convention Center.

“We are deeply honored to present Katie Couric with our Distinguished Public Service Award for her passionate support of cancer research, and her stellar efforts to raise public awareness about cancer prevention and treatment,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “She has provided invaluable education to the general public about cancer through her consistently outstanding reports of breakthroughs in cancer research, and her vital work in screening and early detection has saved countless lives from cancer, especially colon cancer.”

Couric, best known for her on-air reporting, became an advocate in the fight against cancer after losing her husband, Jay Monahan, to colon cancer in 1998. She co-founded the National Colorectal Cancer Research Alliance with the Entertainment Industry Foundation (EIF) to fund cutting-edge research in colorectal cancer in 2000 and famously underwent an on-air colonoscopy to raise awareness of the importance of screening. Her televised colonoscopy is credited with the 20 percent increase in these procedures the same year, which researchers refer to as the “Couric Effect.”

In 2008, Couric co-founded Stand Up To Cancer (SU2C), also an initiative of the Entertainment Industry Foundation, with a group of women whose lives have been deeply affected by cancer. Co-founders and/or members of SU2C’s Council of Founders and Advisors include EIF Board Chair Sherry Lansing, President and CEO Lisa Paulsen, and Senior Vice President Kathleen Lobb; marketing executives Rusty Robertson and Sue Schwartz; cancer survivor and television producer Noreen Fraser; the late filmmaker Laura Ziskin and her producing partner Pam Williams; and non-profit executive Ellen Ziffren. SU2C has raised nearly $200 million in funds predominantly used to provide large grants to Dream Teams of scientists doing research that accelerates the delivery of new therapies to patients. Many AACR members have been beneficiaries of these generous funds that have fostered breakthrough cancer research.

Additionally, Couric co-founded the Jay Monahan Center for Gastrointestinal Health at New York-Presbyterian Hospital and Weill Cornell Medical College in New York, N.Y., a clinical center providing integrated care and focusing on prevention, screening, treatment, support, research and education for people who have, or are at risk for developing, gastrointestinal cancers. She also worked with the University of Virginia to establish the Emily Couric Clinical Cancer Center in honor of her sister, a Virginia state senator, who died of pancreatic cancer in 2001.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Rick Buck
(856) 562-5668
Rick.Buck@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Stand Up To Cancer and the St. Baldrick's Foundation Announce New Pediatric Cancer Dream Team

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

$14.5 Million Grant Over Four Years Will Fund Research Focusing on Novel Therapies for the Most Challenging-to-cure Childhood Cancers

Dream Team Will Use In-kind Donation of Instrumentation to SU2C from Life Technologies Corporation

WASHINGTON, D.C. — Stand Up To Cancer (SU2C) and the St. Baldrick’s Foundation, along with the American Association for Cancer Research (AACR), SU2C’s scientific partner, announced the formation of a Dream Team dedicated to childhood cancer research during a press conference today at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

John M. Maris, M.D., director of the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia, will lead the Dream Team. Crystal L. Mackall, M.D., chief of the Pediatric Oncology Branch of the National Cancer Institute (NCI) in Bethesda, Md., is the co-leader of the project, which is titled “Immunogenomics to Create New Therapies for High-risk Childhood Cancers.”

The SU2C-St. Baldrick’s Pediatric Dream Team Translational Cancer Research Grant will provide $14.5 million in funding over four years for this innovative project that will unite researchers in two highly productive disciplines of translational pediatric cancer research that have historically functioned independently — genomics and immunotherapeutics. Genomics is the detailed analysis of the complete set of DNA within a sample and it can be used to dissect the cause and progression of cancer. Immunotherapeutics is the study and development of treatments that employ the body’s own immune system against disease.

“In the past 20 years, very few new therapies have been developed for pediatric cancer,” said Maris, who is also the Giulio D’Angio endowed professor at the University of Pennsylvania School of Medicine. “This Dream Team has deep expertise in each of the most lethal pediatric cancers and includes thought leaders in the fields of genomics and immunotherapeutics. It is our goal, indeed our expectation, that we will initiate a sustained effort to maximize pediatric cancer cure rates through a genomics-anchored immunotherapeutic program.”

Researchers on this Dream Team represent seven institutions: The Children’s Hospital of Philadelphia, the NCI, the British Columbia Cancer Agency, Baylor College of Medicine, The Hospital for Sick Children in Toronto, Seattle Children’s Hospital and the University of Wisconsin. While researchers at the NCI will be participating fully as members of the Dream Team, in accordance with policy, no funds from the grant are going to the NCI.

“This Dream Team united top-tier researchers across North America in a multidimensional campaign that uses the best of basic science to create new therapeutics while at the same time initiating multiple, cutting-edge clinical trials of immunotherapy for deadly pediatric cancers,” said Mackall. “We are confident that this combined approach will lead to novel therapies that will improve outcomes for some of the most lethal childhood cancers.”

The joint venture between the St. Baldrick’s Foundation, the leading nongovernmental provider of childhood cancer research grants, and SU2C, formed in 2008 to accelerate cancer research, brings together two of the world’s leading cancer research fundraising groups. Formation of the team, the first SU2C Dream Team focused solely on pediatric cancer research, will fulfill the mission of both organizations to fund the most promising research to find cures for childhood cancers and ultimately enable survivors to lead long and healthy lives.

“Every St. Baldrick’s volunteer and donor can be very proud to be a part of funding this Dream Team that has the potential to be a real game-changer in childhood cancer research,” said Kathleen Ruddy, chief executive officer of the St. Baldrick’s Foundation. “This team will use increased knowledge about genomics to find new ways to put the body’s own immune system to work fighting off cancer. It will result in more survivors of not just one type but several very difficult childhood cancers, and a better quality of life for those survivors.”

In addition to the $14.5 million in cash funding, this Dream Team will have access to research instruments and equipment donated by Life Technologies Corporation to SU2C, valued at up to $500,000. Life Technologies is a developer and manufacturer of laboratory instrumentation, including semiconductor-based platforms for sequencing DNA.

“Cancer is devastating, plain and simple, but when it hits children, our hearts break that much more,” said SU2C Co-founder Katie Couric. “We are excited that the new SU2C-St. Baldrick’s Dream Team is focused solely on developing new and better treatments for many of the most deadly pediatric cancers. This will help thousands of children and teens diagnosed each year to not only beat the disease but also to thrive and live long and fulfilling lives.”

The SU2C-St. Baldrick’s Pediatric Translational Cancer Research Project

Curative chemotherapy for cancer was first realized in children and survival rates for many childhood cancers improved dramatically through the last decades of the 20th century. However, those cure rates have plateaued since the 1990s, and for some childhood cancers, cure rates remain below 20 percent. Further, current therapies often lead to severe side effects that reduce the quality of life for patients as they grow into adulthood. New classes of therapeutics are needed if the survival of children with cancer is to be improved and the financial, emotional and life-altering costs of curative therapies are to be decreased.

Genomics and immunotherapeutics are two of the most promising areas in childhood cancer research. Recent advances in cancer genomics have led to new understanding of the genetic basis of some of the most aggressive childhood cancers, but they have not yet revolutionized treatment. In parallel, efforts to harness the body’s own immune system to eradicate cancer have yielded stunning results in some patients, but these treatments remain limited in application, available only for a few cancer types and accessible at only a small number of institutions.

The Dream Team is a collaboration between pediatric cancer researchers in the largely disparate disciplines of cancer genomics and immunotherapeutics. The team will focus on developing new, targeted immunotherapeutics for the most difficult-to-cure childhood cancers.

“This Dream Team brings together an outstanding group of scientists and physicians with complementary skills in genomics and immunotherapy,” said Sung Poblete, Ph.D., R.N., president and chief executive officer of Stand Up To Cancer. “The Team is well poised to identify new immunologic targets in a wide variety of high-risk pediatric tumors, including many of the pediatric hematological malignancies (high-risk leukemias, such as relapsed acute lymphoblastic leukemia and acute myeloid leukemia) and solid tumors, such as medulloblastoma, glioblastoma, neuroblastoma and sarcomas.”

First, the team will create a multi-institutional computing infrastructure to perform new analyses on childhood cancer genomes as well as normal childhood tissues to determine which molecules are on the surface of cancer cells, but not normal cells. Discoveries will be validated using newly created, powerful research tools known as tissue microarrays from cancerous and normal tissues from children.

The team will then create new immunotherapeutic drugs and approaches based on these discoveries in a collaborative manner with the Frederick National Laboratory and industry partners, and perform the necessary laboratory studies to determine if they are promising for testing in children.

In parallel, the team will develop an Immunogenomics Pediatric Cancer Dream Team clinical trials consortium to test the new immunotherapeutics in children. A major goal of the team is to create a mechanism by which these highly specialized therapies can be exported to all children’s hospitals for future testing and clinical application, with the hope that these will be transformative new therapies.

The project is estimated to start July 1, 2013, with the first clinical trials scheduled to open within the first year.

Dream Team Selected Through Unique, Rigorous Process

An SU2C-St. Baldrick’s Joint Scientific Advisory Committee (JSAC) conducted a unique, rapid and rigorous evaluation of the applications via a multistep scientific review process.

The committee is chaired by Nobel Laureate Phillip A. Sharp, Ph.D., institute professor at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology in Cambridge, Mass. It is co-chaired by SU2C representative Lee J. Helman, M.D., scientific director for clinical research at the NCI’s Center for Cancer Research in Bethesda, Md., and the St. Baldrick’s Foundation representative Jeffrey M. Lipton, M.D., Ph.D., director, hematology/oncology and stem cell transplantation and professor of pediatrics and molecular medicine at the Hofstra North Shore-Long Island Jewish School of Medicine in Hempstead, N.Y. The JSAC is comprised of highly accomplished senior laboratory researchers and physician-scientists, as well as advocates.

The review process began with a call for ideas by the AACR in October 2012. The committee then chose four finalist teams, each of which met with the JSAC to present the plans for their research and respond to questions about their projects — a level of interaction between applicants and reviewers that is unique in a scientific review process.

The AACR is responsible for administering the grant and provides ongoing scientific oversight to ensure that progress is being made. Since the launch of Stand Up To Cancer, the AACR has played an integral role as SU2C’s scientific partner by providing scientific leadership, expert peer review and grants administration.

Dream Team Principals and Advocate Members

The “Immunogenomics to Create New Therapies for High-risk Childhood Cancers” Dream Team consists of a multidisciplinary group of experts that includes laboratory and clinical researchers, young investigators and senior scientists who have not worked together in the past, as well as patient advocates. In addition to Maris and Mackall, team members are:

Principals:

Poul Sorensen, M.D., Ph.D., British Columbia Cancer Agency, Vancouver, Canada
Donald W. Parsons, M.D., Ph.D., Baylor College of Medicine, Houston, Texas
Michael D. Taylor, M.D., Ph.D., The Hospital for Sick Children, Toronto, Canada
Michael C. Jensen, M.D., Seattle Children’s Research Institute, Seattle, Wash.
Paul Sondel, M.D., Ph.D., University of Wisconsin, Madison, Wis.

Advocates:

Kelly Cotter, childhood cancer survivor
Jay Scott, Alex’s Lemonade Stand Foundation
Liz Scott, Alex’s Lemonade Stand Foundation
Patrick Sullivan, Team Finn Foundation
Lisa Tichenor, What Would Willy Want Foundation (QuadW Foundation)
Mac Tichenor, QuadW Foundation

Including today’s announcement, SU2C has now awarded grants to 10 Dream Teams and one International Translational Cancer Research Grant. Twenty-six Innovative Research Grants have been awarded to individual young investigators. Together, these recipients comprise more than 500 scientists from 101 institutions.

# # #

About Stand Up To Cancer
Stand Up To Cancer (SU2C) – an initiative of the Entertainment Industry Foundation, a 501(c)(3) non-profit organization – raises funds to hasten the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. SU2C marshals the resources of the media and entertainment industries in the fight against this disease.

Current members of the SU2C Council of Founders and Advisors (CFA) include Talk Show Host, Journalist and well-known Cancer Advocate Katie Couric; Sherry Lansing, Chairperson of the Entertainment Industry Foundation’s Board of Directors and Founder of the Sherry Lansing Foundation; EIF President and CEO Lisa Paulsen; EIF Senior Vice President Kathleen Lobb; Rusty Robertson and Sue Schwartz of the Robertson Schwartz Agency; Pamela Oas Williams, President of Laura Ziskin Productions and Executive Producer of Stand Up To Cancer’s In-house Production Team, and Nonprofit Executive Ellen Ziffren. All current members of the CFA were co-producers of the 2012 televised special. The late co-founder Laura Ziskin executive produced both the Sept. 5, 2008, and Sept. 10, 2010, broadcasts. SU2C was formally launched on May 27, 2008. Sung Poblete, Ph.D., R.N., has served as SU2C’s president and CEO since 2011.

SU2C’s “Dream Team” approach to funding translational cancer research enables scientists from different disciplines at research centers across the country and internationally to collaborate on projects geared toward getting new, less toxic treatments to patients as quickly as possible. Monies also support innovative cancer research projects that are often deemed “too risky” by conventional funding sources. One hundred and one institutions are currently involved. As SU2C’s scientific collaborator, the American Association for Cancer Research, led by a prestigious SU2C Scientific Advisory Committee, provides scientific oversight, expert review of the research projects and grants administration. For more information, visit standup2cancer.org.

About the St. Baldrick’s Foundation
The St. Baldrick’s Foundation is a volunteer-driven charity committed to funding the most promising research to find cures for childhood cancers and give survivors long and healthy lives. St. Baldrick’s coordinates its worldwide signature head-shaving events where volunteers get bald to stand in solidarity with kids fighting cancer and raises money to support research. Since 2005, St. Baldrick’s has awarded more than $103 million to support lifesaving research, making the Foundation the largest private funder of childhood cancer research grants. St. Baldrick’s funds are granted to some of the most brilliant childhood cancer research experts in the world and to younger professionals who will be the experts of tomorrow. Funds awarded also enable hundreds of local institutions to participate in national pediatric cancer clinical trials, which may be a child’s best hope for a cure. For more information about the St. Baldrick’s Foundation please call 1.888.899.BALD or visit www.stbaldricks.org.

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

About Life Technologies
Life Technologies Corporation (NASDAQ: LIFE) is a global biotechnology company that is committed to providing innovative products and services to leading customers in the fields of scientific research, genetic analysis and applied sciences. With a presence in more than 180 countries, the company's portfolio of 50,000 end-to-end solutions is secured by more than 5,000 patents and licenses that span the entire biological spectrum -- scientific exploration, molecular diagnostics, 21st century forensics, regenerative medicine and agricultural research. Life Technologies has approximately 10,000 employees and had sales of $3.8 billion in 2012.

Media Contacts:

Stand Up To Cancer
Jane E. Rubinstein
(212) 843-8287 office
(516) 993-0708 cell
jrubinstein@rubenstein.com

St. Baldrick’s Foundation
Marc McCarthy
(626) 792-8247 x40 office
(626) 344-4625 cell
marc@stbaldricks.org

American Association for Cancer Research
Rick Buck
(215) 446-7162 office
(856) 562-5668 cell
rick.buck@aacr.org

Life Technologies
Suzanne Clancy
(760) 602-4545
(858) 205-4235
Suzanne.clancy@lifetech.com

SU2C's Unique Research Funding Model Yielded Success With First Round of Dream Team Grants

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

Work By the Five Original Dream Teams Has Led to More Than 40 Clinical Trials in Just Three Years

WASHINGTON, D.C. — Stand Up To Cancer (SU2C) and the American Association for Cancer Research, SU2C’s scientific partner, are pleased to announce that the original Dream Team grants awarded by SU2C to five multi-institutional, cross-disciplinary research teams in May 2009, have accelerated cancer research progress that has been translated into meaningful advances for patients with cancer in just three years.

Focusing on epigenetic therapy; the PI3K pathway in women’s cancers; breast cancer; detection and analysis of circulating tumor cells; and pancreatic cancer, these original Dream Teams have made tremendous advances, including:

A new potential treatment strategy whereby cancer patients receive two types of therapy sequentially because the first therapy, which is an epigenetic therapy that is a combination of two drugs, makes cancer cells more sensitive to the second;
Numerous potential novel treatment options for women with breast cancer;
The development of a new, noninvasive way to monitor cancer patients’ responses to treatments in real time; and
The identification of a drug combination that extends the lives of patients with metastatic pancreatic cancer.

Judy DeMarsh, a 66-year old lung cancer patient and a nurse, is one person who has benefited from the new sequential treatment strategy that includes the epigenetic therapy developed by one of the Dream Teams. “Three years after being diagnosed with quite advanced cancer, and I’m still here and feeling great,” said DeMarsh. “The result is better than I could have imagined. I know it’s science, but it feels like a fairy tale, and hopefully other patients will be more encouraged not to give up and to participate in clinical trials. I give my heartfelt thanks to SU2C for funding the epigenetic therapy, to the team of researchers that developed it, and to those researching and developing the immunotherapy.”

In addition to promoting immense scientific and clinical progress, the establishment of the SU2C Dream Teams has shifted the way much clinical cancer research is conducted. Not only are formerly competitive researchers and institutions collaborating, but the “Targeting the PI3K Pathway in Women’s Cancers” Dream Team brokered a rare partnership between pharmaceutical companies: Novartis and AstraZeneca agreed to join forces with the Dream Team and assess the effectiveness of a combination of investigational anticancer drugs, helping achieve SU2C’s goal of getting new treatments to patients faster.

SU2C’s distinctive Dream Team approach to funding cancer research was specifically designed to eliminate barriers to creativity and collaboration, in part, by enabling scientists with different expertise from different institutions across the country — and in some cases, internationally — to work together. Each Dream Team project is translational in nature, designed to move science from “bench to bedside,” where it can benefit patients, as quickly as possible.

A key attribute of the Dream Team funding model is that each Dream Team’s progress is evaluated biannually by a group of three reviewers, typically members of the SU2C Scientific Advisory Committee (SAC) that reviewed the initial Dream Team applications and made recommendations on funding to SU2C. The purpose of these periodic reviews is to ensure that milestones and objectives are being satisfactorily achieved. These reviews also provide a unique level of interactivity between grant recipients and members of the Nobel laureate-led oversight committee that has been pivotal in the successes that the Dream Teams have achieved.

“The unprecedented, collaborative research enabled by Stand Up To Cancer’s Dream Team grants has helped patients in the way that we hoped it might,” said Nobel Laureate Phillip A. Sharp, Ph.D., institute professor at the David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology in Boston, Mass., who chairs the SAC. “The five original Dream Teams are to be commended on the way that they executed their mission with a laser-like focus that allowed them to take scientific advances into the clinic at an extraordinarily quick pace. The fact that the work of these teams of researchers led to the initiation of more than 40 clinical trials over the course of just three years is unparalleled.”

“This is a significant milestone for us, and we are incredibly grateful to everyone who so generously contributed in order to make this happen,” said Sherry Lansing, SU2C co-founder, chairperson of the Entertainment Industry Foundation’s (EIF) Board of Directors and founder of the Sherry Lansing Foundation. “It is truly inspirational to see that the dedication of — and collaboration within — these five teams of incredible scientists has already paid off for patients. It motivates us to work harder in our mission to support this innovative way of promoting groundbreaking research aimed at getting new cancer treatments to patients in an accelerated time frame.”

The original five SU2C Dream Teams are comprised of seven leaders, three co-leaders and 27 principal researchers from more than 40 institutions, with more than 220 individuals participating in total. Each team has at least two members from patient advocacy groups to ensure that the perspectives of the patients and survivors they represent are integrated into the research on an ongoing basis.

The total funding level for the five teams’ first three years of work was $73.6 million. At the recommendation of the SAC, an additional $7.2 million in total funding is being provided to four of these five teams, and the time frames for all of the teams have been extended, by either one or two years.

The teams and the important topics they are pursuing are listed below in alphabetical order according to the leaders’ names:

“Bringing Epigenetic Therapy to the Forefront of Cancer Management.” Leader: Stephen B. Baylin, M.D., deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Co-leader: Peter A. Jones, Ph.D., D.Sc., distinguished professor of urology, and biochemistry and molecular biology at the University of Southern California Norris Comprehensive Cancer Center;
“Targeting the PI3K Pathway in Women’s Cancers.” Leader: Lewis C. Cantley, Ph.D., director of the Cancer Center at Beth Israel Deaconess Medical Center; Co-leader: Gordon B. Mills, M.D., Ph.D., chair of the Department of Systems Biology at The University of Texas MD Anderson Cancer Center;
“An Integrated Approach to Targeting Breast Cancer Molecular Subtypes and Their ‘Resistance’ Phenotypes.” Leaders: Joe W. Gray, Ph.D., chair of the Department of Biomedical Engineering at Oregon Health & Science University, and Dennis J. Slamon, M.D., Ph.D., director of clinical/translational research at UCLA’s Jonsson Comprehensive Cancer Center;
“Bioengineering and Clinical Applications of Circulating Tumor Cell Chip.” Leader: Daniel A. Haber, M.D., Ph.D., director of the Massachusetts General Hospital Cancer Center; Co-leader: Mehmet Toner, Ph.D., professor of biomedical engineering at Harvard Medical School; and
“Cutting Off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer.” Leaders: Craig B. Thompson, M.D., president and chief executive officer, Memorial Sloan-Kettering Cancer Center, and Daniel D. Von Hoff, M.D., distinguished professor and physician-in-chief, The Translational Genomics Research Institute (TGen).

Descriptions of each Dream Team’s work and progress during the initial three-year grant term follow.

Bringing Epigenetic Therapy to the Forefront of Cancer Management

Background:
In many cases, the genetic alterations that drive cancerous cell behaviors work in conjunction with changes in what is known as the cell’s epigenome. The epigenome is the sum of all the chemical, or epigenetic, flags on a cell’s genome that help control whether a gene is turned on or off.

The positioning of epigenetic flags on the genome is not permanent, so it should be possible to reverse the abnormal positioning of epigenetic flags seen in cancer. The overarching goal of the Epigenetic Dream Team was to pursue the exciting potential of attacking cancers using therapies that overturn the epigenetic abnormalities that inappropriately turn genes on or off in cancer cells, thus bringing the promise of epigenetic therapy to the clinic for the benefit of patients with different types of cancer.

Progress:
In its first three years of funding, this Dream Team initiated five clinical trials. These have yielded impressive results for early-stage clinical trials, with vigorous clinical responses with minimal toxicities observed for several patients. They have also identified a novel therapeutic approach that has the potential to change the face of therapy for tens of thousands of cancer patients. The Dream Team is currently in the final stages of designing later-stage trials to validate this novel treatment strategy.

The potential new therapeutic approach is to treat patients with an epigenetic therapy, or a combination of two epigenetic therapies, and then with a conventional chemotherapy or an experimental immunotherapy.

The idea for this unique approach came from observations from one of the phase I/II clinical trials conducted by the Epigenetic Dream Team that suggested that epigenetic therapies can make patients’ tumors more sensitive to subsequent treatments. Specifically, these data showed that a substantial number of patients with recurrent, metastatic, non–small cell lung cancer who did not respond to treatment with the combination epigenetic therapy being tested in the trials, did respond dramatically to subsequent chemotherapy or experimental immunotherapy. The responses observed were far more extensive and durable than expected for patients with advanced, non–small cell lung cancer who had not benefited from previous treatments. Therefore, epigenetic therapy may be used to sensitize cancers for subsequent therapies.

In a first-in-human phase I/II clinical trial conducted by the Epigenetic Therapy Dream Team, a novel epigenetic therapy called SGI-110 has shown promise as a new treatment option for patients with an early form of leukemia, myelodysplastic syndrome, and those with acute myelogenous leukemia.

Aaron Cohen, a 77-year-old acute myeloid leukemia patient, received SGI-110 through the Epigenetic Dream Team clinical trial. “I’ve had a good life, and if this was what God wanted I was OK with it,” Cohen said of his diagnosis. “I was in the process of tidying everything up in my life when I went on the trial. Now my outcome looks wonderful and my outlook on life has changed. I can’t thank the doctors enough. For me, this drug has been a lifesaver.”

Targeting the PI3K Pathway in Women’s Cancers

Background:
The phosphatidylinositide 3 kinase (PI3K) pathway is a complex signaling pathway that, in concert with other signaling pathways, regulates cell survival and growth. Genetic mutations that lead to inappropriate PI3K pathway activity are the most frequently detected cancer-driving mutations in women’s cancers, in particular breast, ovarian and endometrial cancers.

A number of drugs that inhibit the PI3K pathway were developed and are currently in clinical trials. However, only a fraction of patients who enroll in these trials benefit, and it has not been possible to predict which patients will respond positively.

The goal of the PI3K Pathway in Women’s Cancers Dream Team was to discover approaches that could predict which patients with breast, ovarian or endometrial cancer will respond positively to PI3K inhibitors.

Progress:
In its first three years of funding, this Dream Team initiated or participated in 12 clinical trials testing PI3K-targeted therapies as single agents or as part of a combination therapy, and more than 600 patients have been enrolled in these trials to date. One of these clinical trials has provided hope that the SU2C Dream Team model of team science can transform how cancer research is done, by stimulating collaboration between pharmaceutical companies to reduce the length of time it takes to test new therapies in the clinic.

This ongoing phase I clinical trial involves testing a combination of two investigational drugs being developed by different pharmaceutical companies — Novartis’ PI3K inhibitor BKM120 and AstraZeneca’s olaparib, an inhibitor of poly-(ADP-ribose) polymerase (PARP) — in patients with recurrent, triple-negative breast cancer or recurrent, high-grade serous ovarian cancer.

The Dream Team successfully negotiated this collaboration between Novartis and AstraZeneca after generating robust preclinical data suggesting that the combination of BKM120 and olaparib would greatly benefit women with certain types of breast and ovarian cancers.

After the PI3K Pathway in Women’s Cancers Dream Team generated data indicating that breast cancers expressing the estrogen receptor, a hormone receptor involved in driving the growth of these breast cancers, frequently had mutations in a gene tied intimately to the PI3K pathway, the PIK3CA gene, the Dream Team initiated another phase I clinical trial. Currently under way, this clinical trial, testing a combination of BKM120 and letrozole, a drug already used for the treatment of local or metastatic breast cancer that is hormone-receptor positive, is showing promise for postmenopausal patients with hormone receptor-positive, metastatic breast cancer, particularly those whose tumors have PIK3CA mutations.

An Integrated Approach to Targeting Breast Cancer Molecular Subtypes and Their ‘Resistance’ Phenotypes

Background:
During the past few years, it has become clear that breast cancer is not a single disease, but a spectrum of diseases that vary in their biology and response to treatment. The three main subtypes of breast cancer are:

Hormone receptor-positive breast cancer, which includes all breast cancers expressing either, or both, of the hormone receptors (estrogen receptor and progesterone receptor);
HER2-positive breast cancer, which includes all breast cancers in which the HER2 gene is amplified; and
Triple-negative breast cancer, which includes all breast cancers that lack expression of the estrogen receptor, the progesterone receptor and HER2.

As a result of these discoveries, treatment for breast cancer has moved beyond a one-size-fits-all approach to an era in which it is tailored to the biology of a patient’s cancer, as determined by breast cancer subtype. Despite this, many breast cancers eventually develop ways to outsmart these new tailored treatments and are said to have become drug-resistant.

The goal of the Breast Cancer Dream Team was to identify molecular mechanisms that lead to drug resistance in the three major breast cancer subtypes and to identify and validate new drug combinations and targets that can be pursued in clinical trials.

Progress:
In its first three years of funding, this Dream Team conducted preclinical work that led to the initiation of nine clinical trials.

For example, preclinical work by the Dream Team led to the idea that the effectiveness of the drug letrozole, which is used for the treatment of local or metastatic breast cancer that is hormone-receptor positive, might be enhanced by adding the investigational agent PD 0332991, which is being developed by Pfizer, to the treatment regimen.

Recently reported results of the phase II clinical trial of the PD 0332991 and letrozole combination indicated that it provided meaningful benefit to women with advanced, estrogen receptor-positive breast cancer. The combination significantly improved median progression-free survival compared with treatment with letrozole alone: 26.1 months for those receiving the combination versus 7.5 months for those receiving letrozole alone.

A phase III clinical trial testing this combination in patients with advanced estrogen receptor-positive breast cancer was initiated by Pfizer in early 2013.

In addition to being involved in preclinical work resulting in numerous clinical trials, the Breast Cancer Dream Team has undertaken a tremendous bioinformatics effort to integrate a cornucopia of genomic data generated not only by this Dream Team, but by other Dream Teams as well. This initiative has revealed genomic signatures related to drug sensitivity and resistance, as well as prognosis for the three major breast cancer subtypes, suggesting ways to link drugs to cancers with specific genomic signatures.

Bioengineering and Clinical Applications of Circulating Tumor Cell Chip

Background:
Cancers arise within the cells of an organ, such as the breast or pancreas, but predominantly cause death by entering the bloodstream, disseminating throughout the body and spreading — or metastasizing — to the bone, liver, lungs or brain.

Cancer cells that spread from the primary tumor can be found in the blood of patients with cancer. These circulating tumor cells (CTCs) are extraordinarily rare — one per one billion normal cells. The ability to detect and analyze them would allow significant advances in detecting and treating cancers as well as understanding the fundamental mechanisms by which cancers spread.

The goal of the CTC-Chip Dream Team was to develop a noninvasive technology sensitive and reliable enough for physicians to use in the clinic to make cancer treatment decisions.

Progress:
In its first three years of funding, this Dream Team developed a technology that has the potential to revolutionize the ways in which cancers are detected and treated.

The technology is a third-generation microfluidic chip that can isolate CTCs more rapidly and from larger volumes of blood compared with the first- and second-generation models they constructed. In addition, this third generation CTC-Chip, called the CTC-iChip, works in a way that makes the isolated tumor cells available for a wider array of subsequent scientific analyses, providing the possibility of enhanced clinical investigation and potentially leading to improved clinical care for patients with cancer.

In addition, the Dream Team has used the second-generation CTC-Chip in several clinical trials to generate clinical data indicating that this technology could make it possible to noninvasively analyze cancers of the internal organs, including lung, prostate, breast and pancreatic cancers, both at the time of diagnosis and throughout treatment. This would enable clinicians to better match patients to effective therapies and monitor response to treatments.

The second-generation CTC-Chip also provided the Dream Team the opportunity to conduct groundbreaking clinical investigation. Using the technology, the Dream Team have gained new understanding of the mechanisms by which breast cancers metastasize, providing potential biomarkers of disease progression.

The CTC-iChip is being developed in conjunction with Johnson & Johnson.

Cutting Off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer

Background:
As the fourth leading cause of cancer death in the United States, pancreatic cancer remains one of the most deadly forms of cancer. More than 80 percent of patients die within the first year of diagnosis. Recent advancements have had little impact, and a new approach is desperately needed.

Most cancer cells are addicted to a continual supply of specific nutrients to produce the energy they need for growth and survival. Researchers have suggested the possibility of “starving” cancer cells to death by depriving them of the nutrients they require for survival and growth.

The overall goal of the Pancreatic Cancer Dream Team was to improve survival for patients with advanced, metastatic pancreatic cancer by first identifying the nutrients pancreatic cancer cells require to fuel their growth and survival, and then developing ways to cut off the fuel supplies.

Progress:
In its first three years of funding, this Dream Team designed and implemented a series of clinical trials testing a drug being developed by Celgene Corporation, a special form of the drug paclitaxel — nanoparticle paclitaxel (Abraxane). The impressive results of the phase III clinical trial were released in January 2013: Patients with metastatic pancreatic cancer receiving the investigational drug in combination with the standard-of-care chemotherapy gemcitabine lived significantly longer than those receiving gemcitabine alone.

In the phase III clinical trial, the investigational drug combination resulted in a 59 percent increase in one-year survival compared with gemcitabine alone (35 percent vs. 22 percent). It also more than doubled two-year survival (9 percent vs. 4 percent). In addition, in the earlier-stage clinical trials the Dream Team observed that the investigational drug combination caused high rates of tumor shrinkage and this enabled patients who had not been able to have potentially curative surgery to have that surgery.

The Dream Team also developed a novel approach to analyzing pancreatic cancer. Using biopsies from tumors removed during surgery, they have identified new metabolic pathways (fuel supplies) involved in tumor growth that represent potential new therapeutic targets.

------------------------------------------------------

Stand Up To Cancer’s major contributors include founding donor Major League Baseball, which has committed more than $30 million and provides countless opportunities to build the Stand Up To Cancer grassroots movement by encouraging fans all over the country to get involved; and Sidney Kimmel, the country’s largest individual contributor to cancer research. Other major SU2C donors include Bloomberg Philanthropies, Cancer Research Institute, Cancer Treatment Centers of America, Genentech, MasterCard, Melanoma Research Alliance, Prostate Cancer Foundation, The Safeway Foundation, Sean Parker Foundation, St. Baldrick’s Foundation, Wallis Annenberg and The Annenberg Foundation, Amgen, GlaxoSmithKline, Pfizer, Oakland A’s Owner/Managing Partner Lew Wolff, Comcast, Inter-American Development Bank (IDB), Philips Electronics, Steve Tisch, The Island Def Jam Music Group and many others.

# # #

About Stand Up To Cancer
Stand Up To Cancer (SU2C) – an initiative of the Entertainment Industry Foundation, a 501(c)(3) non-profit organization – raises funds to hasten the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. SU2C marshals the resources of the media and entertainment industries in the fight against this disease.

Current members of the SU2C Council of Founders and Advisors (CFA) include Talk Show Host, Journalist and well-known Cancer Advocate Katie Couric; Sherry Lansing, Chairperson of the Entertainment Industry Foundation’s Board of Directors and Founder of the Sherry Lansing Foundation; EIF President and CEO Lisa Paulsen; EIF Senior Vice President Kathleen Lobb; Rusty Robertson and Sue Schwartz of the Robertson Schwartz Agency; Pamela Oas Williams, President of Laura Ziskin Productions and Executive Producer of Stand Up To Cancer’s In-house Production Team, and Nonprofit Executive Ellen Ziffren. All current members of the CFA were co-producers of the 2012 televised special. The late co-founder Laura Ziskin executive produced both the Sept. 5, 2008, and Sept. 10, 2010, broadcasts. SU2C was formally launched on May 27, 2008. Sung Poblete, Ph.D., R.N., has served as SU2C’s president and CEO since 2011.

SU2C’s “Dream Team” approach to funding translational cancer research enables scientists from different disciplines at research centers across the country and internationally to collaborate on projects geared toward getting new, less toxic treatments to patients as quickly as possible. Monies also support innovative cancer research projects that are often deemed “too risky” by conventional funding sources. One hundred and one institutions are currently involved. As SU2C’s scientific collaborator, the American Association for Cancer Research, led by a prestigious SU2C Scientific Advisory Committee, provides scientific oversight, expert review of the research projects and grants administration. For more information, visit standup2cancer.org.

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contacts:

Stand Up To Cancer
Jane E. Rubinstein
(212) 843-8287 office
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American Association for Cancer Research
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Rick.Buck@aacr.org

jrubinstein@rubenstein.com

Biomarkers Discovered That May Help Predict Response to Drugs Targeting KRAS-mutated NSCLC

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

Effective targeted treatments for NSCLC with KRAS mutations are lacking.
MEK/PI3-kinase inhibitor combination is a promising treatment for this type of cancer.
Use of biomarkers could help guide treatment decisions.

WASHINGTON, D.C. — Scientists have identified biomarkers that may help predict whether patients with KRAS-mutated non-small cell lung cancer (NSCLC) will respond to concurrent treatment with an MEK inhibitor and a PI3 kinase inhibitor, a drug combination currently being investigated in ongoing clinical trials. The discovery was made as part of a study presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10, by Aaron N. Hata, M.D., Ph.D., a clinical fellow at the Massachusetts General Hospital in Boston.

Although several targeted therapies have been developed for patients with NSCLC, there are currently no proven targeted treatments for patients with NSCLC that harbors a KRAS mutation, which accounts for 20 percent to 25 percent of all NSCLC cases.

“Treatment with an MEK inhibitor and PI3 kinase inhibitor is a combination targeted therapy that may be effective for some patients with KRAS-mutant NSCLC, but it is not likely to be effective for all patients with this form of cancer,” said Hata. “We want to be able to know which patients are going to respond to this combination therapy so that we can identify them and tailor their treatment accordingly.”

To explore response to MEK and PI3 kinase inhibitors, Hata and colleagues studied a variety of NSCLC cell lines that all had mutated KRAS. They found that some of the cancer cell lines responded to the drug combination by undergoing a process of cell death called apoptosis, whereas others did not.

“Our results were not surprising from the standpoint that induction of cell death is known to be important for response of cancer cells to therapy,” Hata said. “What was surprising was the difference in apoptosis among the cell lines.”

Specifically, lack of a cell death response to the combination of MEK and PI3 kinase inhibitors correlated with the decreased expression of pro-cell death mediators and the upregulation of anti-cell death regulators.

“We found that three specific proteins predicted response,” Hata said. “Two of them, the BIM and PUMA proteins, induced cell death, and the third, the BCL-XL protein, inhibited cell death.”

In addition, prior research has shown that many KRAS-mutant lung cancers also have a mutation in the TP53 gene, and the protein that it generates, P53, is known to be involved in the cell death process. In this study, the researchers found that TP53 mutation status did not predict response to the MEK/PI3 kinase inhibitor combination, but it did affect how the cells underwent cell death.

“Our research so far has focused on human cancer cell lines,” Hata said. “We do not yet know if these correlations will hold true in patients.”

Ideally, Hata and his colleagues would like to determine whether the proteins they identified are predictive of patient response to MEK/PI3 kinase inhibitors in the clinic.

“The ultimate goal would be having the ability to measure levels of these proteins in patients before they go on treatment,” Hata said. “If they have favorable levels, that would tell us they are likely to respond to this treatment, and if they do not, it would be better to select a different treatment.”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Next-generation PI3 Kinase Inhibitor Demonstrated Early Efficacy, Safety

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

The drug GDC-0032 demonstrated a favorable safety profile in a phase I clinical trial.
The agent showed promising activity in PI3 kinase alpha-mutant tumors.

WASHINGTON, D.C. — GDC-0032, a potent, next-generation PI3 kinase inhibitor, demonstrated early signs of efficacy for patients with cancers driven by mutations in the PI3 kinase alpha gene, according to first in-human results presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“We’ve shown that this novel agent is well tolerated,” said Dejan Juric, M.D., lead investigator of the study at the Termeer Center for Targeted Therapies at Massachusetts General Hospital in Boston. “We’ve shown that the safety profile is favorable and that the side effects are predictable. Early results show that the drug has very promising activity, particularly in tumors that have activating mutations in PI3 kinase alpha.”

GDC-0032, which is being developed by Genentech, a member of the Roche Group, targets a family of molecules called PI3 kinases. The drug is distinguished by its enhanced in-vitro activity against the mutant form of the family member called PI3 kinase alpha, which is known to be present in approximately 40 percent of hormone receptor-positive breast cancers.

“We currently have no approved therapies that directly target this critically important component of cancer cells,” Juric said.

This phase Ia, multicenter, open-label study included 34 patients with locally advanced or metastatic solid tumors who received a once-daily dose of GDC-0032. Researchers tested five dosing cohorts: 3 mg, 5 mg, 8 mg, 12 mg and 16 mg.

The drug was well tolerated, and side effects consisted of hyperglycemia, diarrhea, fatigue and nausea. The only study-related grade 4 adverse event was hyperglycemia in the 16-mg dose cohort, according to Juric.

“Those are very common and predictable side effects,” he said. “In particular, hyperglycemia is a so-called ‘on-target’ side effect because PI3 kinase alpha plays an important role in glucose metabolism. All agents that effectively block PI3 kinase alpha lead to some level of glucose elevation.”

The results also showed that four of six patients with breast cancers driven by a PI3 kinase alpha mutation had a partial response according to RECIST criteria, which is an objective measure of tumor shrinkage, according to Juric. In addition, the researchers observed a partial response in one patient with lung cancer driven by a PI3 kinase alpha mutation, as well as objective tumor shrinkage in a patient with HER2-amplified breast cancer.

“This trial is an important step forward in getting us closer to developing an agent that shuts down PI3 kinase alpha effectively,” Juric said. “It is impressive how frequently PI3 kinase alpha mutations are found in human cancers. This is one of the first agents to have shown selectivity and encouraging signs of efficacy when we target that particular mutation.”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

AKT Inhibitor AZD5363 Well Tolerated, Yielded Partial Response in Patients With Advanced Solid Tumors

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

The AKT signaling pathway is often involved in cancer development and drug resistance.
AZD5363 inhibits AKT and is effective against tumor cells with mutations in the PI3K pathway.
Two phase I studies showed the drug was well tolerated; partial response and stable disease were achieved.

WASHINGTON, D.C. — The investigational drug AZD5363, which has shown activity in preclinical studies, was well tolerated in humans, and two patients with advanced solid tumors showed partial response, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“PI3K/AKT signaling is very important in cancer cells,” said Udai Banerji, M.D., Ph.D., clinical senior lecturer at the Institute of Cancer Research and The Royal Marsden NHS Foundation Trust in London, United Kingdom. “This signaling pathway is highjacked by abnormalities or mutations in genes that can cause a normal cell to behave like a cancer cell.”

AZD5363 is a new-generation drug inhibiting the three forms of the AKT protein: AKT1, AKT2 and AKT3. It has shown promising results in several tumor cell lines and animal studies. In prior clinical trials, AKT inhibitors have almost always been tested in continuous dosing schedules, resulting in excessive toxicity, according to Banerji.

Banerji and colleagues conducted two phase I studies and administered AZD5363 to the patients in two schedules: continuous dosing seven days a week and intermittent dosing with four days on and three days off.

Among the 92 patients recruited thus far, an intermittent dosing schedule of 480 mg twice a day was generally well tolerated. Side effects included high blood sugar, rash and diarrhea. “But what is important about these side effects, such as raised blood sugar, is that these are known consequences of targeting the AKT pathway,” said Banerji. “This provides proof of principle that the drug is working.”

Using pharmacokinetics studies, the team determined that the dose achieved in the patients’ blood was comparable to the dose used in preclinical studies in which they saw positive outcomes. More than 30 percent reduction was seen in the levels of two proteins, pPRAS40 and pGSK3 beta, in plucked hair and blood samples collected from the patients, suggesting that the drug successfully inhibited AKT.

One patient with ovarian cancer and one with cervical cancer showed partial response to treatment. Both had a mutation in either AKT1 or PIK3CA in their cancers. A third patient with ovarian cancer with a PIK3CA mutation had prolonged stable disease.

“What is very gratifying is that a response like this to a single agent is not something we see very often,” said Banerji. “Also, these data support the growing realization that AKT inhibitors are beneficial when administered intermittently and not continuously.”

Encouraged by these results, AstraZeneca recently initiated two phase Ib studies with patients with prostate and breast cancers. AZD5363 was discovered by AstraZeneca subsequent to collaboration with Astex Therapeutics and its collaboration with The Institute of Cancer Research.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Intermittent Treatment With Vemurafenib May Prevent Lethal Drug Resistance in Melanoma

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

Late-stage melanomas develop resistance to vemurafenib treatment.
Treatment cessation decreased tumor growth in patients with vemurafenib-resistant melanoma.
An intermittent treatment regimen may help overcome drug resistance.

WASHINGTON, D.C. — Vemurafenib-resistant tumors in patients with melanoma showed reduced growth after cessation of treatment, and in animal models, drug resistance was prevented by intermittent treatment, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“It was exciting to witness the discovery of BRAF mutations in melanoma and the translation of this discovery into an effective therapy with vemurafenib,” said Darrin Stuart, Ph.D., senior research investigator at the Novartis Institutes for Biomedical Research in Emeryville, Calif. “It was, however, disappointing to see patients stop responding to such a promising therapy after six to eight months of treatment.”

BRAF mutations are found in more than half of all cases of melanoma, and previous studies have shown vemurafenib increases survival for these patients, according to Stuart. However, most patients relapse with lethal, drug-resistant disease.

In a previous study to investigate the mechanisms causing melanomas to become resistant to vemurafenib, Stuart and his colleagues grew patient-derived tumors expressing BRAF mutations in mice and demonstrated that not only do these tumors develop vemurafenib resistance, but they become dependent on the drug to grow. Tumors stopped growing and regressed after cessation of the drug in these animals.

To evaluate whether the drug dependency observed in animals is seen in humans as well, Stuart and his team collaborated with colleagues who evaluated 42 patients with vemurafenib-resistant tumors at the Royal Marsden Hospital in London, United Kingdom. Computed tomography scans of the tumors taken after cessation of treatment were available for 19 patients. Of these patients, 14 showed a decrease in the rate of their tumor growth.

“This is the first evidence that the drug-addicted state that we observed in our mouse models may also occur in humans,” said Stuart.

He and his colleagues also implanted mice with human patient-derived tumors and treated them with vemurafenib either continuously or intermittently — four weeks on and two weeks off. They found that none of the tumors in animals assigned to intermittent dosing developed drug resistance.

“Continuous dosing maintained the selective pressure required for the few surviving tumor cells to develop resistance, and alternating the selective pressure through intermittent dosing appeared to prevent the evolution and expansion of resistant cells,” said Stuart. “This study provides insight into how vemurafenib-resistant tumors evolve. Alternative dose regimens could prolong the durability of response to vemurafenib in BRAF-mutant melanoma.”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
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Novel Drug Combination Showed Antitumor Activity in Patients With Incurable BRCA-deficient Cancers

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

Patients received sapacitabine and seliciclib as sequential treatments.
Several patients with BRCA mutations achieved disease response or experienced prolonged stable disease.
BRCA mutation carrier status may be a potential biomarker for response.

WASHINGTON, D.C. — When given sequentially, two orally available experimental drugs — sapacitabine and seliciclib — worked together to elicit antitumor effects in patients with incurable BRCA-deficient cancers, according to phase I data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10. There are no drugs yet approved specifically for this patient population.

“Since we began to enroll predominantly patients who carried a BRCA mutation in the study, we have seen several responses among those patients, as well as instances of prolonged stable disease lasting more than a year,” said Geoffrey Shapiro, M.D., Ph.D., associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School in Boston, Mass.

Shapiro and colleagues initially designed the phase I study to exploit preclinical results that suggested that sapacitabine and seliciclib worked together synergistically. Sapacitabine is an oral nucleoside analogue that induces single-strand damage to DNA. If the damaged DNA is not repaired, it ultimately results in cell death. Repair of sapacitabine-induced DNA damage requires BRCA proteins, suggesting that BRCA-deficient cancers may be particularly sensitive.

Seliciclib inhibits cyclin-dependent kinases (CDKs); CDK inhibition has been shown to augment cancer cell death induced by drugs like sapacitabine by multiple mechanisms, in part by suppressing DNA repair pathways.

Researchers enrolled 38 patients with incurable solid tumors and adequate organ function. They assigned patients to treatment with sapacitabine twice daily for seven days followed by seliciclib twice daily for three days.

Four patients with BRCA-deficient pancreatic, breast or ovarian cancers had confirmed ongoing partial responses to the drug combination. Three patients are experiencing partial responses, with the longest lasting more than 78 weeks.

Furthermore, researchers observed stable disease of 12 weeks or more in eight additional patients, including two patients with ovarian and breast cancers who carried the BRCA mutation and whose stable disease lasted 64 weeks and 21 weeks, respectively.

The maximum tolerated doses were 50 mg sapacitabine twice daily and 1,200 mg seliciclib twice daily. Dose-limiting toxicities included reversible transaminase elevations and neutropenia. Adverse events were mild to moderate in intensity.

Results of skin biopsies after treatment showed a 2.3-fold increase in DNA damage induced by sapacitabine, as measured by gamma-H2AX immunohistochemistry. Additional DNA damage occurred after treatment with seliciclib with a 0.58-fold further increase in gamma-H2AX staining.

“Initially in the dose-escalation phase of the trial, this combination produced stable disease of modest duration in some patients, which has been the experience with sapacitabine and CDK inhibitors in solid tumors,” Shapiro said. “However, other published research during the course of the study indicated the role of the homologous recombination pathway, dependent on BRCA proteins, for repair of sapacitabine-induced DNA damage. Additionally, the CDK proteins were implicated in DNA repair pathways. These findings prompted us to enroll patients with advanced cancer who had the BRCA mutation and led to the first partial responses and instances of durable stable disease.”

Based on these emerging results, Shapiro and colleagues continue to enroll appropriate patients in the trial, where the combination has been most efficacious. Additional schedules of the combination therapy are under evaluation. According to Shapiro, if further work continues to confirm BRCA mutation status as a potential biomarker for response, these drugs, both individually and in combination, should ultimately be evaluated in larger groups of patients who carry BRCA mutation. If successful, these drugs may provide an important treatment alternative for patients with BRCA-deficient cancers.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Preclinical Study Indicates Potential for Novel Inhibitor to Overcome Drug Resistance Induced by RAF, MEK Inhibitors

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

The therapy targets ERK, a component of the MAPK pathway.
The therapy led to tumor regression in mice.
A phase I study of the investigational ERK inhibitor is under way.

WASHINGTON, D.C. — A new class of investigational medicines may help to treat patients with cancers driven by mutations in genes such as BRAF or KRAS/NRAS, including those patients who have become resistant to therapies that target BRAF directly, according to preclinical data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

These new drugs, which are being developed by Merck, target ERK proteins. ERK proteins are components of the MAPK signaling pathway. In this pathway, they function downstream of RAS, BRAF and MEK. Inhibitors of BRAF and MEK have shown clinical efficacy in patients with melanoma harboring BRAF gene mutations.

“The MAPK pathway has been the subject of intense research to develop inhibitors against components of the pathway for the treatment of cancer,” said Ahmed Samatar, Ph.D., team leader of discovery oncology at Merck Research Laboratories. “Unfortunately, tumor responses are often transient and resistance to therapy is commonly associated with pathway reactivation involving the downstream module ERK1/2.”

Samatar and colleagues hypothesized that inhibiting ERK in tumor cells driven by an activated MAPK pathway, as a result of either BRAF or RAS mutations, could provide a means of inhibiting tumor cell growth. The researchers used SCH772984, a novel ERK inhibitor, to test this theory.

Their results indicated that SCH772984 was a potent inhibitor of ERK1/2 in cultured human tumor cells with mutations in BRAF, NRAS or KRAS. The drug also induced tumor regression when tested in mouse models.

In addition, SCH772984 inhibited MAPK signaling and cell proliferation in human tumor cells resistant to BRAF and MEK inhibitors alone or in combination.

“Patients with cancer treated with BRAF and/or MEK inhibitors are susceptible to the development of resistance primarily via reactivation of ERK,” Samatar said. “ERK inhibitors may provide a means to treat patients with these drug-resistant tumors, and an ERK inhibitor in combination with a BRAF or MEK inhibitor may also provide a strategy to overcome drug resistance.”

Samatar and colleagues have initiated a phase I clinical trial of an investigational ERK inhibitor in patients with solid tumors.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Novel Serum Biomarker Bilirubin Predicted Lung Cancer Risk in Smokers

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

Serum metabolites are emerging biomarkers for lung cancer detection.
Bilirubin identified by metabolomic profiling had biomarker potential.
Men who were smokers and had low bilirubin levels had increased risk for cancer incidence and mortality.

WASHINGTON, D.C. — Smokers with low bilirubin levels were at increased risk for lung cancer incidence and mortality compared with those who had the highest bilirubin levels, making serum bilirubin a potential biomarker for lung cancer risk prediction, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“Although it was expected that bilirubin may be protective against lung cancer incidence and mortality, we were somewhat surprised that the effect of bilirubin was only evident in smokers, which will have profound public health implications, given that 90 percent of lung cancers occur in smokers,” said Xifeng Wu, M.D., Ph.D., professor and chair of the Department of Epidemiology at The University of Texas MD Anderson Cancer Center in Houston.

Most patients with lung cancer are diagnosed at inoperable advanced stages and the prognosis is particularly dismal, with the five-year survival rate for stage 3b and stage 4 diseases being 5 percent and 1 percent, respectively, according to Wu. Biomarkers are urgently needed for improving risk prediction for lung cancer beyond smoking variables, and serum metabolites are emerging as promising markers.

Wu and colleagues used a unique multiphase study design for the metabolomics profiling of serum samples. In the initial discovery phase, the researchers recruited 20 healthy individuals, 20 patients with early-stage non-small cell lung cancer and 20 patients with late-stage non-small cell lung cancer, matched for age and gender. They performed global, unbiased metabolite profiling using the serum from patients’ blood samples. They then validated the top three differentially expressed metabolites in the next phase involving two additional populations with a total of 519 healthy individuals and patients with non-small cell lung cancer.

The metabolite bilirubin emerged as the most promising marker, and the researchers further validated this finding in the third phase, which included a large Taiwanese prospective cohort of 435,985 individuals.

Among the Taiwanese cohort, the researchers found a 7.02 incidence rate of lung cancer per 10,000 person-years for men with bilirubin levels of 0.68 mg/dL or less, compared with an incidence rate of 3.73 among men whose bilirubin levels were 1.12 mg/dL or more. This translates into a 51 percent increase in the risk for developing lung cancer for patients with low bilirubin. Researchers also found a lung cancer-specific mortality rate of 4.84 for men with the lowest levels of bilirubin compared with a mortality rate of 2.46 for men with the highest bilirubin levels — a 59 percent increase in lung cancer-specific mortality among those with the lowest bilirubin levels.

Looking only at smokers, Wu and her colleagues found that those with the lowest levels of bilirubin had a 69 percent increase in the risk for lung cancer development and a 76 percent increase in mortality compared with smokers with the highest levels of bilirubin. In contrast, there was no significant effect of bilirubin in “never-smokers.”

The association between bilirubin levels and lung cancer was only significant in “ever-smokers” and men, according to Wu.

“The ability to use low bilirubin to identify higher-risk smokers, over and above the number of ‘pack years’ smokers report having smoked, has significant public health impact in reducing lung cancer burden,” said Wu. “Low levels of bilirubin, established as an objective risk index for lung cancer incidence and mortality, may be viewed by smokers as an urgent health warning to drive them to quit.”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

KDM1 May Represent a New Therapeutic Target for Glioma

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

The protein KDM1 was overexpressed in gliomas.
KDM1 inhibition reduced glioma cell proliferation in vitro.
KDM1 inhibition reduced glioma growth in a mouse model.

WASHINGTON, D.C. — Researchers have generated preclinical data demonstrating that the protein KDM1, which functions as a lysine demethylase, is a potential target for glioma treatment, according to Gangadhara R. Sareddy, Ph.D., a postdoctoral fellow in the Vadlamudi Laboratory at The University of Texas Health Science Center in San Antonio, who presented the results at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“We found that KDM1 expression is upregulated in gliomas and have preclinical evidence that suggests pharmaceutical inhibition of the KDM1 axis could have therapeutic implications for the treatment of gliomas,” said Sareddy.

Gliomas, the deadliest form of primary central nervous system neoplasms, represent about 70 percent of brain tumors, according to Sareddy. Roughly 20,000 patients are diagnosed with gliomas each year in the United States.

“Patients with malignant gliomas have a survival time of approximately 14 months,” Sareddy said. “Novel therapies are urgently needed. Evolving evidence suggests that glioma development is a multistep process that results from changes both in genetic and epigenetic mechanisms. Unlike genetic alterations, epigenetic changes are reversible; therefore, targeting epigenetic changes represents a promising therapeutic approach.”

He and his colleagues set out to assess the importance of KDM1 in gliomas. Through immunohistochemical analysis, they found that KDM1 expression was elevated in gliomas. They silenced KDM1 expression with siRNA or inhibited it with pargyline or NCL-1 and found that reducing its expression or inhibiting it pharmacologically reduced glioma cell line growth in vitro. In addition, inhibiting KDM1 pharmacologically reduced the growth of patient-derived primary glioblastoma multiforme cells in vitro and the growth of a human glioma cell line in mice.

Results of mechanistic studies demonstrated that inhibiting KDM1 increased the expression of tumor suppressor p53 target genes through epigenetic modifications, according to Sareddy.

“Because KDM1 plays a critical role in glioma biology and because epigenetic modifications are reversible, pharmacological inhibition of KDM1 could be a potential therapy for gliomas,” Sareddy said. “Identification of KDM1 as a therapeutic agent can be readily extended to clinical use with current chemotherapies, providing an additional tool for enhancing survival in patients with glioma.”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Older Women Who Delay Mammography Screening More Likely to Die From Breast Cancer

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

Time from last mammogram to diagnosis significantly affected breast cancer mortality for women diagnosed after age 75.
Data suggest a role for continued mammography screening in older women.

WASHINGTON, D.C. — Older women with an extended period of time between their last mammogram and breast cancer diagnosis were at an increased risk for breast cancer mortality, suggesting a role for continued mammography screening among women aged 75 years and older, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“We found that for women age 75 and older, a longer time interval between the last mammogram and the date of breast cancer diagnosis was associated with a greater chance for dying from breast cancer,” said Michael S. Simon, M.D., M.P.H., leader of the breast multidisciplinary team at Barbara Ann Karmanos Cancer Institute in Detroit, Mich., and professor of internal medicine and oncology at Wayne State University School of Medicine.

To evaluate whether time between mammograms affected breast cancer mortality, Simon and colleagues analyzed data from 8,663 women in the Women’s Health Initiative observational study or clinical trial who had been diagnosed with breast cancer during a 12.2-year follow-up.

An interval of five or more years between a woman’s last mammogram and breast cancer diagnosis was associated with advanced-stage disease in 23 percent of women compared with 20 percent of women with an interval of six months to a year, a statistically significant difference, which may affect large numbers of women.

In an adjusted analysis, researchers found a longer interval between mammogram and diagnosis was associated with a significantly increased risk for breast cancer mortality among women aged 75 or older at diagnosis. Women aged 75 years or older at diagnosis who had an interval of five years or more between mammogram and diagnosis or who had never had a mammogram had a threefold greater risk for death from breast cancer compared with women who had an interval of six months to a year between mammogram and diagnosis. These relationships were not found among younger women.

“I am not sure why we are seeing these results particularly for older women. Tumors of younger women were more likely to be a little more unfavorable overall,” Simon said. “It is possible that the differences in the relationship between screening interval and mortality in older versus younger women may be related to the more aggressive nature of the tumors in younger women, which might obliterate the effects of more screening. Other reasons may include differences in cancer treatment, information that was not available for this cohort of women.”

According to Simon, physicians should discuss the risks and benefits of mammography with older patients and encourage them to continue mammography screening. “Our findings suggest that regular mammography should be continued for older women every one or two years; however, as with younger women, mammography screening should be considered in light of the overall health of the individual woman,” he said.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

BRAF Mutation Less Common Among Patients With Melanoma in Ireland

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

Data showed melanoma-driving mutations vary by demographic area.
Different treatment options are required for patients without a BRAF mutation.
c-MET mutation was found in 12 percent of Irish patients.

WASHINGTON, D.C. — The BRAF mutation believed to drive disease in about half of patients with melanoma was found to occur at a significantly lower frequency in patients with melanoma in Ireland, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

The study, which included two independent cohorts of patients in Europe, revealed that only about 20 percent of a cohort of Irish patients with melanoma harbored a BRAF mutation.

“The clinical approval of a BRAF inhibitor that blocks the function of the mutant BRAF protein is currently one of the most promising approaches to treat metastatic melanoma,” said William M. Gallagher, Ph.D., associate professor of cancer biology at the UCD Conway Institute in Dublin, Ireland. “The observation of a reduced BRAF mutation rate in Irish patients directly influences future treatment strategies for these patients.”

Gallagher and colleagues investigated cancer-related changes in 33 genes known to be of key importance in cancer development. They evaluated two independent cohorts of patients with melanoma, including 94 patients from Ireland and 60 patients from Belgium.

Researchers found that 21 percent of patients with melanoma from Ireland had a BRAF mutation compared with 52 percent of the Belgian patients.

The currently approved BRAF inhibitor specifically targets the BRAFV600E mutation; therefore, the researchers also analyzed the percentage of patients carrying this specific BRAF mutation. They found that 19 percent of the Irish patients had the BRAFV600E mutation compared with 43 percent of the Belgian patients. They found similar results after analyzing tumor tissue from three additional independent cohorts of patients with melanoma from Ireland. In these three groups of 137 patients, 79 patients and 34 patients, the researchers found the BRAFV600E mutation in 21 percent, 20 percent and 32 percent of patients, respectively.

“Treatment with the clinically approved BRAF inhibitor that blocks the function of the mutant BRAF protein will only be applicable to patients who possess the relevant BRAFV600E mutation,” Gallagher said. “As a result, the majority of Irish patients with melanoma will not benefit from this therapy and are currently left without good alternative treatment possibilities.”

Although the exact reason for this difference is unknown, Gallagher offered some explanations. First, it is known that BRAF and NRAS mutations are mutually exclusive, and he and his colleagues found a higher rate of NRAS mutations among the Irish patients compared with the patients from Belgium (21 percent versus 13 percent).

In addition, 12 percent of Irish patients had a mutation in the c-MET gene; none of the Belgian patients did. A mutation in c-MET has rarely been found in melanoma before, according to Gallagher.

“This study shows that the molecular biology underlying melanoma can change in different demographic areas,” Gallagher said. “Hence, to be able to give patients the best possible treatment, we need to take into account the molecular variations, or genomic landscape, contributing to tumor development and progression between different populations.”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

AACR Launches New Journal: Cancer Immunology Research

registration@aacr.org () — Sun, 07 Apr 2013 12:00:00 GMT

Launch Issue Available Online and in the Annual Meeting Exhibit Hall

PHILADELPHIA — The American Association for Cancer Research has announced the electronic launch of its newest journal, Cancer Immunology Research, which will publish groundbreaking original articles on major advances in cancer immunology. A print preview issue is being distributed at the AACR Annual Meeting 2013, taking place April 6–10 at the Walter E. Washington Convention Center in Washington, D.C.

The journal will publish research articles reporting major advances in all areas of the discipline of cancer immunology, including basic investigations in host–tumor interactions, developmental therapeutics in model systems, early translational studies in patients and late-stage clinical trials. In addition to research articles, review articles and commentaries, the journal will include special features such as “Masters of Immunology,” which will be primers by leading immunologists, and “Cancer Immunology at the Crossroads,” which will be perspectives that highlight the relationship between immunology and other areas of cancer research and medicine.

“The AACR continuously strives to educate its members and the public about the most cutting-edge and relevant research to supports its goals of prevention and curing cancer,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “Cancer Immunology Research is an excellent addition to the AACR’s robust group of cancer publications, and I am confident it will capture the most significant work in the field of cancer immunology, and inspire thinking that will accelerate the pace of breakthroughs.”

Glenn Dranoff, M.D., professor of medicine at Dana-Farber Cancer Institute in Boston, Mass., is the founding editor-in-chief of Cancer Immunology Research. He is also the Harvard Medical School leader for the Dana-Farber/Harvard Cancer Center Program in Cancer Immunology. Dranoff has devoted much of his career and research efforts to understanding the mechanisms underlying the stimulation of tumor immunity and to applying these discoveries to the development of cancer vaccines.

“Cancer Immunology Research will play a leading role in educating the greater cancer research community regarding the principles and opportunities in cancer immunology,” said Dranoff. “Recent clinical successes have validated the longstanding idea that therapeutic manipulation of the immune system may achieve meaningful antitumor effects.

“My vision is that by disseminating knowledge of cancer immunology, this journal will catalyze cross-disciplinary work that yields a deeper understanding of the host–tumor relationship, more potent cancer treatments and improved clinical outcomes,” he added. “The launch of CIR has generated considerable enthusiasm in the cancer research community, and this is reflected in the outstanding didactic perspectives and original research articles to be published in the inaugural issue. This high level of scholarship and impact will be characteristic of CIR.”

Specific topics of interest for publication include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies and clinical investigations.

Cancer Immunology Research is the eighth peer-reviewed scientific journal to be added to the AACR’s publications portfolio. The AACR also publishes a magazine for cancer survivors, patients and their caregivers.

# # #

AACR and CRI Honor Dr. James Allison With First Lloyd J. Old Award in Cancer Immunology

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — James P. Allison, Ph.D., professor and chair of the Department of Immunology in the division of basic science research at The University of Texas MD Anderson Cancer Center in Houston, will receive the newly established cancer immunology award from the American Association for Cancer Research (AACR) and the Cancer Research Institute (CRI) in honor of his innovative research in the field of cancer immunology.

Allison will receive the award at a reception on Saturday, April 6 at 7 p.m. in the Constitution Ballroom in the Walter E. Washington Convention Center. He will present his lecture, “Mobilizing the Immune System for Cancer Therapy,” on Wednesday, April 10 at 10 a.m. in Ballroom A-B in the convention center.

“I’m delighted and honored to be given this award named for Lloyd Old, who is widely considered to be the father of cancer immunotherapy. I was fortunate in knowing Dr. Old as a mentor, but also as a close friend. This new award by the AACR and CRI recognizes individuals, but it’s also a gratifying recognition of the growing prominence of immune therapy and of our progress toward fulfilling Dr. Old’s goal of unleashing the immune system against cancer,” Allison said.

The first annual AACR-CRI Lloyd J. Old Award in Cancer Immunology was established in honor of the late Lloyd J. Old, M.D., who is considered the “Father of Modern Tumor Immunology.” Old’s outstanding research in the field of cancer immunology, as well as his decades of leadership in fostering the field, has had a far-reaching impact on cancer. The award is intended to recognize an active cancer immunologist who, like Old, has done outstanding and innovative research in cancer immunology that has had a far-reaching impact on the field.

“Dr. Allison is a thought leader in the field of immunology,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “We owe him for much of our understanding of the mechanisms regulating the immunological responses mediated by the T cells. He laid the foundation for our ability to manipulate the T-cell system for therapeutic applications against cancers, and is, therefore, greatly deserving of this honor.”

“James Allison’s work has provided a roadmap for connecting the laboratory and the clinic and moving discovery into real-world applications that can save the lives of patients,” said Jill O’Donnell-Tormey, Ph.D., chief executive officer and director of scientific affairs at CRI. “As someone on the cutting edge of cancer immunotherapy, Dr. Allison embodies the vision that Lloyd Old had for the field and the hope of one day harnessing the immune system’s power to conquer cancer.”

Allison’s early research focused on understanding how the immune system defends the body from pathogens and cancers, with particular emphasis on the role of T-cells. In this process, he uncovered the previously unknown mechanisms of the functions of T-cells. In 1982, he and his colleagues identified the T-cell antigen receptor (TCR), which recognizes foreign antigens. He also discovered that this recognition is not sufficient for the activation of naïve T-cells. Subsequently, he discovered two key molecules, CD28, which is constitutively expressed on the surface of the T-cell and is needed for its activation, and a homolog of CD28 called CTLA-4, which is induced after the activation of the T-cell, and is a major down-regulator of T-cells. Allison described how all these molecules act in concert in the process of engaging the antigen-presenting cells that carry the foreign antigens, such as cancer antigens.

Allison hypothesized that the immune system fails to recognize tumor cells since CTLA-4 down-regulates T-cell activation. Based on this theory, he created antibodies to this molecule and demonstrated the rejection of established tumors in several mouse model systems. He then developed an antibody to human CTLA-4, ipilimumab, which has been used in clinical trials in more than 4,000 patients with a variety of cancers including metastatic melanoma and prostate, renal, lung and ovarian cancers. A randomized, blinded phase III trial with metastatic melanoma resulted in the survival of 25 percent of the patients for four years. No other drug has shown a prolongation of life in similar trials for this disease. Ipilimumab was approved by the U.S. Food and Drug Administration in 2011.

In recent years, Allison identified several other checkpoint and costimulatory molecules and he has been testing the combination of immunological therapies and targeted therapies, such as tyrosine kinase inhibitors, for more effective treatment against cancers. He will play an instrumental role in MD Anderson’s recently announced Moon Shots Program to dramatically accelerate the pace of converting scientific discoveries into clinical advances that reduce cancer deaths.

Allison has received numerous awards and honors, including the Lifetime Achievement Award of the American Association of Immunologists, the Centeon Award for Innovative Breakthroughs in Immunology, the William B. Coley Award for Distinguished Research in Basic and Tumor Biology from the CRI, The Dana Foundation Award in Human Immunology Research, the Richard V. Smalley Award from the International Society for Biological Therapy of Cancer and the Roche Award for Cancer Immunology and Immunotherapy. He is a member of the American Association for Immunologists, the Academy of Cancer Immunology, the National Academy of Sciences and the American Association for the Advancement of Science, among others.

Allison obtained his doctoral degree in biological sciences from The University of Texas in Austin and did his postdoctoral fellowship in molecular immunology at Scripps Clinic and Research Foundation in La Jolla, Calif. He served as the chair of the immunology program at the Memorial Sloan-Kettering Institute from 2004 to 2012.

###

Media Contacts:

AACR
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org

CRI
Brian M. Brewer
(212) 688-7515, ext. 242
bbrewer@cancerresearch.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information, visit www.AACR.org. Follow the AACR on Twitter: @aacr #aacr. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.

About the Cancer Research Institute
The Cancer Research Institute (CRI), a nonprofit established in 1953, is the global leader in cancer immunology and immunotherapy. Since its inception, CRI has invested hundreds of millions of dollars to support research conducted by more than 3,000 scientists and clinicians worldwide to understand the immune system and how it can be harnessed to conquer all cancers. This work has laid the foundation for nearly every major cancer immunotherapy breakthrough over the past half century. Guided by an international panel of the world’s leading immunologists and cancer immunologists, including three Nobel laureates and 29 members of the U.S. National Academy of Sciences, CRI provides essential funding to support every stage of discovery, from laboratory investigation to clinical trials of the most promising cancer immunotherapies for patients. CRI also sponsors a seminal international symposium on cancer immunology each year, hosts annual scientific colloquia dedicated to overcoming challenges in immunotherapy research and development, forges collaborative partnerships between academia and industry to facilitate the development pathway for novel immunotherapeutics, and presents special recognition awards to individuals who have made outstanding contributions to cancer research, patient care and public awareness. Through its sustaining support and leadership in the field, CRI is accelerating the development of safe and effective immunotherapies that stand to revolutionize the treatment of all cancers. For more information, visit http://cancerresearch.org or follow CRI on Twitter @CancerResearch.

Dr. Hagop Kantarjian Receives the 18th Annual AACR Joseph H. Burchenal Memorial Award

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — Hagop M. Kantarjian, M.D., will receive the 18th Annual AACR Joseph H. Burchenal Memorial Award for Outstanding Achievement in Clinical Cancer Research at the American Association for Cancer Research Annual Meeting 2013, held in Washington, D.C., April 6-10. Kantarjian is chair of the leukemia department and a professor of medicine at The University of Texas MD Anderson Cancer Center in Houston.

The award is presented to a scientist who has made outstanding achievements in clinical cancer research. Kantarjian’s lecture, “Leukemia Research and Progress – A Look Back at the Future,” will take place on Tuesday, April 9, at 4 p.m. ET in Ballroom A-B in the Walter E. Washington Convention Center.

“I am truly honored and humbled to be in the company of great men and women who, by their dedication to clinical research, have made seminal discoveries that have led to seismic changes in our understanding of cancer biology and therapeutics,” said Kantarjian. “As with many individual awards, this honor also reflects the efforts and accomplishments of MD Anderson’s Department of Leukemia, which includes outstanding investigators across the full spectrum of leukemia.”

Kantarjian, who is also the Kelcie Margaret Kana research chair in the leukemia department and associate vice president for global academic programs at The University of Texas MD Anderson Cancer Center, has contributed to numerous changes in the treatment of patients with several forms of leukemia. For example, he was a leader in the development and testing of both the first- and second-generation inhibitors of the BCR-ABL protein that drives nearly all cases of chronic myeloid leukemia (CML). These treatments significantly reduced the mortality rate for patients with chronic myeloid leukemia from 10 to 15 percent, to 1 to 2 percent.

His research on acute lymphoid leukemia (ALL) led to several advances in patient care, including the establishment of standard-of-care treatment for patients diagnosed with the disease and the U.S. Food and Drug Administration (FDA) approval of clofarabine for children with acute lymphoid leukemia that has recurred after, or failed to respond to, initial treatment.

In addition, Kantarjian’s research established the efficacy of epigenetic therapy for myelodysplastic syndrome (MDS), a potentially lethal blood malignancy that also frequently develops into acute myeloid leukemia (AML), and led to the concept of low-intensity therapy for patients older than 70 with acute myeloid leukemia. He also led the clinical trial that resulted in the January 2012 FDA approval of ruxolitinib for myelofibrosis, a type of chronic leukemia for which there was no specific treatment. As well as being the first drug approved for myelofibrosis, ruxolitinib was the first drug targeting the cancer-driving protein JAK2 to be approved by the FDA.

Kantarjian’s significant contributions to the leukemia community extend far beyond his own research achievements. He has established a world-renowned department of leukemia at The University of Texas MD Anderson Cancer Center and mentored many internationally recognized experts in the field of clinical leukemia research. Research and clinical trials by the department have been instrumental in discovering new, more effective combination treatments and in FDA approval of new drugs for CML, MDS and AML, ALL and myelofibrosis. Additionally, two of the eight programs chosen for MD Anderson’s Moon Shots Program are from the department. One addresses chronic lymphocytic leukemia and the other both MDS and AML.

Kantarjian received his medical degree from The American University of Beirut in Lebanon and then completed a fellowship at The University of Texas MD Anderson Cancer Center. He has received numerous accolades throughout his career, including the Outstanding Service to Mankind Award from the Leukemia Society of America.

Kantarjian, a member of the AACR since 1985, was on the editorial board of Clinical Cancer Research and serves on the boards of several other scientific journals. He is also a member of several other professional organizations, including the American Association for the Advancement of Science, the American Society of Hematology and the American Society for Clinical Oncology, where he also serves on the board of directors. He has authored or co-authored more than 1,000 peer-reviewed medical publications.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Dr. Guillermina Lozano Honored With the 16th Annual AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) will award the 16th Annual AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship to Guillermina Lozano, Ph.D., professor and chair of the Department of Genetics at The University of Texas MD Anderson Cancer Center in Houston, for her contributions toward the current understanding of the regulation of the p53 tumor suppressor pathway.

Lozano’s lecture, “Activities of Mutant p53 Proteins in Cancer,” will take place on Saturday, April 6 at 5:15 p.m. ET in Ballroom C in the Walter E. Washington Convention Center.

The AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship was established in 1998, in honor of renowned virologist Charlotte Friend, Ph.D., for her discovery of the Friend virus and her pioneering research on viruses, cell differentiation and cancer. The lectureship recognizes an outstanding scientist who has made meritorious contributions to the field of cancer research and who has, through leadership or by example, furthered the advancement of women in science.

“I am honored to be in the company of other distinguished scientists who have previously received the Charlotte Friend Memorial Lectureship Award, and I am inspired by the courage and resourcefulness of the woman for which it was named. Charlotte Friend was an accomplished scientist most renowned for her discovery of the Friend leukemia virus in 1956. She was also a creative and instinctive scientist who had fun doing science. She will continue to serve as one of my role models as I strive to solve the complexities of the p53 tumor suppressor pathway and hopefully, in turn, serve as an example for other women in science,” Lozano said.

Lozano’s research has been critical in clarifying the physiological significance of regulation of the tumor suppressor p53 to cancer development and in highlighting the potential for exploiting this knowledge for cancer treatment. She was the first researcher to identify a transactivation domain in the p53 tumor suppressor, which led other researchers to the identification of the genes controlled by p53. She also demonstrated the critical role that Mdm2 and Mdm4 have in restraining p53 activity and conducted the seminal work that established the importance of p53’s dual role as gatekeeper, or inhibitor of cell growth, and caretaker, or stabilizer of the genome, in preventing tumor development.

Using a mouse model of Li-Fraumeni syndrome, a condition that predisposes patients to early onset of several cancers as a result of inheriting a p53 genetic mutation, Lozano substantiated the idea that distinct p53 mutations in human patients cause cancer in different ways. She followed this work with a series of studies comparing the characteristics of normal and mutant p53. Collectively, the findings in this area of her research have significant implications for the development of therapies for the more than 50 percent of human cancers with a mutation in p53 and emphasize the need to more completely understand these mutations to determine the best course of treatment for individual patients.

She has collaborated with clinical investigators to develop a mouse model that more closely mimics human metastatic lung adenocarcinoma than previous mouse models. This improved mouse model is being used in preclinical studies of preventive and therapeutic agents against lung cancer. She has also collaborated with orthopedic oncologists to create a mouse model to study the formation of sarcomas.

Lozano previously received the 2011 AACR-Minorities in Cancer Research Jane Cooke Wright Lectureship and the University of Medicine and Dentistry of New Jersey (UMDNJ)-Graduate School of Biomedical Sciences Distinguished Alumnus Award. She has served on several AACR committees, including as chair of the Laboratory Research Awards Selection Committee, as a member of the Research Grant Review Committee and as a member of the 2012 Annual Meeting Program Committee. Lozano is currently an editorial board member for Molecular Cancer Research. Additionally, she has served on several study sections of the National Institutes of Health.

She received her doctorate in biochemistry from Rutgers University and the UMDNJ in Piscataway, N.J., and completed postgraduate training in molecular biology at Princeton University in Princeton, N.J.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

AACR Recognizes Grantees at the Annual Meeting 2013

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) will honor 22 new grant recipients at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

The AACR will congratulate the recipients at a grants reception and dinner on Tuesday, April 9, at 6:30 p.m. ET in the Walter E. Washington Convention Center.

Fellowships:
2013 AACR-Amgen Inc. Fellowships in Clinical/Translational Cancer Research

Kara N. Maxwell, M.D., Ph.D.; University of Pennsylvania
“Identification of Clinically Relevant Breast Cancer Susceptibility Variants”
Victoria E. H. Wang, M.D., Ph.D.; University of California, San Francisco
“The Role of the c-Met/HGF Pathway in Drug Resistance and Metastasis”

2012 AACR Anna D. Barker Fellowship in Basic Cancer Research

Amélie Griveau, Ph.D.; University of California, San Francisco
“Phosphorylated-Olig2 Biochemical Function in Pediatric Glioma”

2013 AACR-Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research

Jian Li Campian, M.D., Ph.D.; Johns Hopkins University
“The Effect of IL-7 on Treatment-related Lymphopenia in High-grade Gliomas”

2013 AACR Judah Folkman Fellowship for Angiogenesis Research

Fusanori Yotsumoto, M.D., Ph.D.; Sanford-Burnham Medical Research Institute
“Stromal Control of Brain Tumor Angiogenesis and Progression by NG2-PG”

2013 AACR-Millennium Fellowship in Lymphoma Research

Michael Pourdehnad, M.D.; University of California, San Francisco
“Novel Mechanisms of mTOR Inhibitor Efficacy in Myc-positive Lymphomas”

2013 AACR-Millennium Fellowship in Prostate Cancer Research

Eliezer M. Van Allen, M.D.; Dana-Farber Cancer Institute
“Dissecting Clinical Response and Resistance to Abiraterone Acetate”

2013 Fight Colorectal Cancer-AACR Fellowship, in memory of Lisa Dubow

Maria Pia Morelli, M.D., Ph.D.; The University of Texas MD Anderson Cancer Center
“Detecting/Predicting Acquired Chemotherapy Resistance in Colorectal Cancer”

2013 QuadW-AACR Fellowship for Clinical/Translational Sarcoma Research

Mohit Sachdeva, Ph.D.; Duke University Medical Center
“miR-182 in Sarcoma: Metastasis Biomarker and Target for Radiosensitization”

Fellows Grant:
2012 AACR-FNAB Fellows Grant for Translational Pancreatic Cancer Research

Olorunseun O. Ogunwobi, M.D., Ph.D.; University of Florida
“Mechanisms of Metastasis in Pancreatic Cancer”

Career Development Awards:
2013 AACR-Aflac Inc. Career Development Award for Pediatric Cancer Research

Yiping He, Ph.D.; Duke University Medical Center
“Role of the MLL2-REST Link in Medulloblastoma Pathogenesis”

2013 AACR-Genentech BioOncology Career Development Award for Cancer Research on the Family Pathway

Hanna Yoko Irie, M.D., Ph.D.; Mount Sinai School of Medicine
“Novel Strategies to Overcome HER2 Targeted Therapy Resistance”

2013 AACR-National Brain Tumor Society Career Development Award

Markus David Siegelin, M.D.; Columbia University Medical Center
“CP-d/n-ATF5 as a Novel Potent Treatment for Malignant Glioma”

2012 Fight Colorectal Cancer-AACR Career Development Award, in memory of Lisa Dubow

Andrea Bertotti, M.D., Ph.D.; Istituto per la Ricerca e la Cura del Cancro, Candiolo, Italy
“Improving Targeted Therapy in Colorectal Cancer Through Xenopatients”

2013 AACR Gertrude B. Elion Cancer Research Award:

Sandra S. McAllister, Ph.D.; Brigham and Women’s Hospital
“Elucidating the Pathophysiology of Disseminated Tumor Cells”

Grants for Independent Investigators:
2013 AACR Dharma Master Jiantai Innovative Grant for Lung Cancer Research

David B. Shackelford, Ph.D.; University of California, Los Angeles
“Develop Novel Therapeutic Strategies to Target LKB1-deficient Lung Cancer”

2012 Breast Cancer Research Foundation-AACR Grants for Translational Breast Cancer Research

Dennis Hallahan, M.D.; Washington University in St. Louis
“Antibodies to Novel Inducible Antigens in Breast Cancer”

Mark Moasser, M.D.; University of California, San Francisco
“A Next-Generation Approach for Inactivation of the HER2-HER3 Tumor Driver”

Stephanie Pero, Ph.D.; University of Vermont and State Agricultural College
“A Novel Ultra HTS Cytotoxic Assay for Discovery of Human Cancer Antibodies”

Shizhen Emily Wang, Ph.D.; Beckman Research Institute of the City of Hope
“Identify Blood-borne microRNAs Associated With Breast Cancer Metastasis”

2012 Caring for Carcinoid Foundation-AACR Grant for Carcinoid Tumor and Pancreatic Neuroendocrine Tumor Research

Eric K. Nakakura, M.D., Ph.D.; University of California, San Francisco
“Overcoming Resistance to mTOR Inhibition in Pancreatic Neuroendocrine Tumor”

2013 Caring for Carcinoid Foundation-AACR Grant for Carcinoid Tumor and Pancreatic Neuroendocrine Tumor Research

Gabriele Bergers, Ph.D.; University of California, San Francisco
“Implication of Heterogeneous Innate Immune Cells in PNET Resistance”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

AACR and Landon Foundation INNOVATOR Awards Support the Next Generation of Researchers

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) and the Kirk A. and Dorothy P. Landon Foundation will present three INNOVATOR Awards at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

The Sixth Annual Landon Foundation-AACR INNOVATOR Award for Cancer Prevention Research will be presented to Kenneth Y. Tsai, M.D., Ph.D., of The University of Texas MD Anderson Cancer Center in Houston.
The Sixth Annual Landon Foundation-AACR INNOVATOR Award for International Collaboration in Cancer Research will be presented to David P. Carbone, M.D., Ph.D., of The Ohio State University in Columbus. Carbone’s collaborator is Carlos Gil Ferreira, M.D., Ph.D., of the Brazilian National Cancer Institute in Rio de Janeiro.
The Fourth Annual Landon Foundation-AACR INNOVATOR Award for Research in Personalized Cancer Medicine will be presented to Nikhil Wagle, M.D., of the Dana-Farber Cancer Institute in Boston, Mass.

The AACR will honor the award recipients at a grants reception and dinner on Tuesday, April 9, at 6:30 p.m. ET in the Independence Foyer and Independence F-I in the Walter E. Washington Convention Center.

The Landon Foundation-AACR INNOVATOR Awards, established in 2008, are designed to foster innovation and collaboration in cancer research and support independent investigators early in their careers. The awards focus attention on younger researchers and recognize the critical need to identify and support the next generation of top cancer researchers who may facilitate breakthroughs in treatment and prevention.

The Landon Foundation-AACR partnership continues with these INNOVATOR Awards, which honor pioneers in cancer research. Including this year’s awards, a total of six prevention, six international collaboration and four personalized medicine awards have been presented. Combined with the previous scientific achievement awards, the total contribution of the Landon Foundation-AACR partnership is nearly $4 million.

Awardees each receive a two-year grant for $100,000 over the grant term.

2013 Landon Foundation-AACR INNOVATOR Award for Cancer Prevention Research

The INNOVATOR Award for Cancer Prevention Research supports a junior faculty researcher conducting research in any discipline of cancer prevention.

Tsai’s project is titled “Genomic Analysis of Cutaneous Squamous Cell Carcinoma Progression.” Skin cancer is the most common class of malignancy in humans and is highly preventable. In the United States, there are over 3 million cases of skin cancer each year. Cutaneous squamous cell carcinoma (SCC) comprises 15 to 20 percent of cases and progresses from a precancerous lesion, actinic keratosis (AK). An understanding of the cellular events that lead from normal skin, to precancerous AK, to malignant cutaneous SCC is very poor and represents a fundamental gap in the understanding of this progression sequence.

Although most molecular genetic studies of AK have centered on known tumor suppressor genes, Tsai proposes to identify important cellular changes and genetic events that determine the progression from irradiated skin to precancerous AK, and from AK to malignant cutaneous SCC using novel approaches.

Ultimately, the goal of this work is to identify robust biomarkers of risk for AK and of progression to cutaneous SCC, and to identify therapeutic targets for chemoprevention at multiple stages of progression. The benefit of this is not only to identify and effectively treat individuals most at risk, but also to identify individuals who do not need aggressive treatment and constant surveillance.

2012 Landon Foundation-AACR INNOVATOR Award for International Collaboration in Cancer Research

The Award for International Collaboration in Cancer Research supports an established international cancer research collaboration involving institutes in multiple countries by supplementing existing funding and providing the means to facilitate travel, training in new techniques and disseminating scientific knowledge gained from the collaboration.

Carbone’s project, “Molecular Profile of Lung Adenocarcinoma in Brazil,” will be part of a continuing international collaboration between American- and Brazilian-based laboratories to better understand the molecular profile of lung cancer in the Brazilian population, which affected more than 27,000 Brazilians in 2012 alone.

A formal collaboration was established in October 2012, between The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and the Richard J. Solove Research Institute in Columbus, Ohio, and the Brazilian National Cancer Institute to establish, in a comprehensive manner, the molecular profile of lung adenocarcinoma in Brazil. This collaboration is the foundation for the work proposed by Carbone.

Carbone and team will develop and validate a customized panel to genotype lung adenocarcinoma; they will then identify the frequency of genetic alterations in tumor specimens from 400 Brazilian patients with diagnosed lung adenocarcinoma. This information will be used to examine the occurrence of genetic changes to clinical and epidemiological characteristics and to also understand genetic clues about ancestry and their relation to genetic alterations in tumors.

This grant will support the continued study of the molecular profile of lung adenocarcinoma in Brazil. Ultimately, this study should provide genetic criteria to help treat Brazilian patients.

2012 Landon Foundation-AACR INNOVATOR Award for Research in Personalized Cancer Medicine

The Award for Research in Personalized Cancer Medicine provides support for a physician-scientist who conducts meritorious studies that hold promise for near-term patient benefit to accelerate progress in the area of personalized cancer medicine.

Wagle’s project, “Systematic Genomic Profiling of Endocrine-resistant Breast Cancer,” may lead to information that fosters the development of more detailed therapeutic treatments that target the core of the cancer as well as those associated with resistance. The information gained from this work may also guide future development of effective therapeutic regimes and provide additional targets for drug development.

Although a clear reduction in recurrence and mortality has been achieved for breast cancer, certain subtypes of the disease remain prevalent and deadly. Up to 40 percent of early-stage breast cancer patients who receive a combination approach to treatment, which includes endocrine therapy, will eventually relapse with resistant disease. Furthermore, if the cancer metastasizes, the eventual development of resistance to endocrine therapy is inevitable. This metastatic, estrogen receptor (ER)-positive breast cancer, which has progressed through endocrine-based therapy, results in the most common cause of breast cancer death. Unfortunately, the underlying reasons for the resistance remain unknown.

This project proposes to examine the genetic makeup of patients who have relapsed with resistant breast cancer and to identify why the resistance to treatment occurred.

The underlying hypothesis for this work is that resistance to hormonal therapy in ER-positive breast cancer involves changes in the patients’ cells that can be understood by studying their tumors’ genetics. Wagle will examine the patients’ tumor cells from pretreatment to when they became resistant to therapy, and analyze the genetic changes that occurred in order to identify alterations that can be targeted with new or existing therapeutic agents.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

About the Kirk A. and Dorothy P. Landon Foundation
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, including the Landon-AACR INNOVATOR Awards.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

More Accurate Markers Identified for Detecting Response to Epigenetic Drugs for Myelodysplastic Syndromes

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

The currently used marker has demonstrated inaccuracy.
Researchers identified and verified two biomarkers.
Findings could lead to a simple urine test to detect the effectiveness of epigenetic drug treatment.

WASHINGTON, D.C. — Researchers have identified and validated two DNA methylation markers that could help physicians to more accurately determine a patient’s response to epigenetic drugs for treatment of myelodysplastic syndromes (MDS), according to Xiaojing Yang, Ph.D., a postdoctoral fellow at the University of Southern California, Los Angeles, who presented the data at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“The current feedback from physicians is that they cannot tell if a patient is really getting the epigenetic drug they are being treated with or not, which makes it difficult for them to decide whether to stop treatment or increase the dosage of the drug,” said Yang. “This pushed us to think, why? Why didn’t the current marker work and should we try to seek a better one?”

These drugs, called DNA methyltransferase inhibitors (DNMTi), work by turning on genes that suppress cancer development, according to Yang. In patients with MDS, these genes are often silenced by the attachment of chemicals called methyl groups to the DNA backbone of the gene (an epigenetic modification made through a process called methylation), and DNMTi prevent methyl group attachment to DNA.

Currently, measuring methylation changes in DNA sequences known as LINE-1 elements is widely used as a predictor of whether or not DNMTi are working, but recent research has found that LINE-1 remethylation after a DNMTi is withdrawn occurs faster than in other regions. This implies that LINE-1 methylation changes may not reflect overall demethylation effects of DNMTi, according to Yang.

Yang and colleagues sought to find improved markers of DNA methylation status. Using the Infinium DNA methylation platform, they assessed the methylation profile of 27,000 genomic regions. The team tested this methylation profile on both normal and tumor bladder tissue samples and on white blood cells from healthy donors. They identified 1,429 regions that were consistently methylated in all three samples.

They then tested the methylation profile of these 1,429 regions in T24 bladder cancer and HL60 leukemia cell lines treated with a DNMTi for 24 hours. Of these, 79 significantly responded to demethylation treatment and remained demethylated beyond 30 days. Further analysis focused on the top two regions, which showed consistent hypermethylation in normal and tumor samples.

To verify their findings, Yang and colleagues studied the DNA demethylation levels of those two markers in urine samples from seven patients with MDS treated with the DNMTi azacitidine. They found that the two markers were significantly demethylated, in contrast to LINE-1 methylation, which showed no clear decreasing trend.

According to Yang, these findings could lead to the use of a simple urine test for detecting response to a DNMTi.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Black Women Had Worse Breast Cancer Mortality Regardless of Cancer Subtype

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

Black women had worse survival compared with other racial/ethnic groups.
They were more often diagnosed with less treatable cancer subtypes.
The survival difference was not attributable entirely to differential subtype diagnosis.

WASHINGTON, D.C. — Black women with breast cancer had significantly worse survival compared with other racial and ethnic groups across cancer subtypes, which suggests that the survival differences are not solely attributable to the fact that black women are more frequently diagnosed with less treatable breast cancer subtypes, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“The results seem to indicate that although African-American women are more likely to be diagnosed with less treatable subtypes of breast cancer compared with white women, it is not the only reason they have worse breast cancer mortality,” said Candyce Kroenke, M.P.H., Sc.D., research scientist at Kaiser Permanente Division of Research in Oakland, Calif.

Kroenke and colleagues examined the link between race and breast cancer survival in a prospective cohort of 1,688 breast cancer survivors enrolled in the Life After Cancer Epidemiology and Pathways study. The survivors had been treated for luminal A, luminal B, basal-like or HER2-enriched breast cancer.

The researchers obtained participants’ self-reported race information from mailed questionnaires. They tested samples of the patients’ tumors to determine their molecular subtype of cancer.

After 6.3 years of follow-up, 499 women had died, 268 of them from breast cancer. Consistent with previous data, black women were nearly two times more likely to have died from breast cancer compared with white women. In addition, black women were less likely to be diagnosed with either the luminal A or luminal B breast cancer subtypes compared with white women.

“African-Americans were more likely to have the hard-to-treat triple-negative breast cancer subtype and had a lower likelihood of having the luminal A subtype, which tends to be the most treatable subtype of breast cancer and has the best prognosis,” Kroenke said.

However, the researchers found that poor prognosis among blacks appeared consistent across breast cancer subtypes. Compared with white women, black women were 2.3 times more likely to die from the luminal A breast cancer subtype, 2.6 times more likely to die from the luminal B subtype, 1.3 times more likely to die from the basal-like subtype and 2.4 times more likely to die from the HER2-enriched subtype.

“African-Americans with breast cancer appeared to have a poorer prognosis regardless of subtype,” Kroenke said. “It seems from our data that the black–white breast cancer survival difference cannot be explained entirely by variable breast cancer subtype diagnosis.”

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Screening Blood Samples for Cancer-driving Mutations More Comprehensive Than Analyzing Traditional Tumor Biopsy

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

Sophisticated test of DNA in blood yielded a more informative summary of cancer mutations.
Testing blood provided a more complete picture than probing tumor samples from the same patient.
Blood-based summary of mutations could help tailor targeted treatments.
Test has the potential to become standard part of cancer care.

WASHINGTON, D.C. — Researchers using a tool called BEAMing technology, which can detect cancer-driving gene mutations in patients’ blood samples, were able to identify oncogenic mutations associated with distinct responses to therapies used to treat patients with gastrointestinal stromal tumors (GIST), according to a researcher who presented the data at the AACR Annual Meeting 2013, held in Washington D.C., April 6-10.

Data from a subanalysis of the phase III GIST–Regorafenib In Progressive Disease (GRID) trial indicated that this blood-based screening technology may provide physicians with a real-time, comprehensive picture of a patient’s tumor mutations, according to George D. Demetri, M.D., director of the Ludwig Center at Dana-Farber Cancer Institute and Harvard Medical School in Boston, Mass.

“Our results show that it is possible to sum the total of all of the heterogeneity in a cancer and get a clear picture of the entire tumor burden, using a simple blood sample,” Demetri said.

In this era of targeted cancer therapies, the goal is to focus cancer treatments on a specific molecular target. However, as researchers discover more about cancers and their heterogeneity, they are finding many patients have anywhere from one to dozens of different mutations in their tumors.

“It is a real issue that when you do a biopsy on one tumor, and then biopsy a different tumor in that same patient a few inches away or on the other side of the body, you may get a different answer when you do the molecular analysis,” Demetri said. “With this blood test, you get a robust summary statement about all the different mutations present across the different tumors in the body. I believe this testing technology has promise to become a standard part of care in the next five to 10 years.”

Data from the main analysis of the phase III GRID study showed that the molecularly targeted drug regorafenib significantly improved progression-free survival compared with placebo for patients with GIST. The researchers hope these results will ultimately lead to the drug’s approval by the U.S. Food and Drug Administration (FDA), according to Demetri. The drug is intended to treat patients with advanced GIST whose disease has failed to be controlled by the only two other FDA-approved therapies for GIST, imatinib and sunitinib (Sutent).

Demetri and colleagues conducted an exploratory analysis on patients in the GRID study to assess GIST genotypes. They isolated DNA from archival tumor tissue, which was then analyzed for mutations in two genes, KIT and PDGFRA, which generate the cancer-driving proteins that are the targets of imatinib, sunitinib and regorafenib. The researchers believed that primary mutations would be detectable using traditional analysis, but that those mutations that developed after treatment with imatinib and sunitinib would not be detectable. They then took blood samples drawn at study entry after failure of both imatinib and sunitinib, and analyzed them for mutations via BEAMing technology.

Mutations in the KIT gene were detected in 60 percent of the blood samples compared with 65 percent of the tumor tissue samples. However, when focusing their analysis on secondary KIT mutations, which are the mutations that drive resistance to targeted therapies like imatinib and sunitinib, the researchers found mutations in 48 percent of blood samples compared with only 12 percent of tissue samples. In addition, nearly half of blood samples in which secondary KIT mutations were found harbored multiple secondary mutations.

Importantly, regorafenib was clinically active compared with placebo in patients with secondary KIT mutations.

According to Demetri, the results show a clear association between the presence of different cancer-driving gene mutations in patients’ blood samples and clinical outcomes.

“By using this technology, we hope to develop the most rational drug combinations and better tests to match patients with the most effective therapies going forward,” Demetri said.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
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Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

Comprehensive Genomic Analysis Identified Alterations in Head and Neck Cancer That Could Lead to Targeted Therapy

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

Study was part of The Cancer Genome Atlas.
Head and neck squamous cell carcinoma was found to be genomically heterogeneous.
Many genomic alterations were shared with other squamous tumors.
Data could lead to new targeted therapies.

WASHINGTON, D.C. — Not all head and neck squamous cell carcinomas (HNSCCs) have the same pattern of genomic alterations, but those cancers with certain distinctive patterns could be amenable to specific targeted therapies, according to a researcher who presented the data at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

The study was part of The Cancer Genome Atlas (TCGA), a National Institutes of Health project to catalog the genetic alterations responsible for several types of cancer, in particular those with a poor prognosis.

“It is likely our study will become a landmark research tool for HNSCC for many years as the secrets included in this massive data set are gradually unlocked,” said David N. Hayes, M.D., M.P.H., an associate professor at the University of North Carolina (UNC), who practices otolaryngology at the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Hayes and colleagues conducted comprehensive genomic analysis of tumor tissue and healthy tissue from 279 patients with previously untreated HNSCC. Eighty percent of the patients reported a history of smoking.

The researchers identified more than 30 sites of significant somatic copy number alteration, or sites of significant change in the number of copies of a certain gene or genetic region. Most of the sites were identical to those recently identified in lung squamous cell carcinoma.

“HNSCC is a tobacco-related cancer,” Hayes said. “We frequently see very altered genomes in other tobacco-related tumors. One of the striking things we observed was a high degree of similarity to other squamous tumors, including lung squamous cell carcinoma. Lessons learned from studying the similarities and differences between tumors, such as these copy number alterations, will be one of the angles researchers will follow to better understand the pathways altered in cancer.”

The researchers also identified differences in alterations between tumors infected with the human papillomavirus (HPV) and those that were negative for the virus. “The current report greatly clarifies an observation that has been made in smaller cohorts of patients with HNSCC that EGFR gene amplification is infrequent in tumors that are infected with HPV but that these same tumors have a high rate of PIK3CA gene mutations,” Hayes said.

This finding raises questions about the efficacy of the EGFR inhibitor approved by the U.S. Food and Drug Administration for the treatment of metastatic HNSCC in patients with HPV-positive tumors, according to Hayes. “It also suggests that these patients may benefit from treatment with the inhibitors of PIK3CA that are in development,” he added. “However, any treatment conclusions should be based on treatment data, which were not part of the TCGA study.”

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Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
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Novel Two-step Immunotherapy Showed Promise for Patients With Recurrent Ovarian Cancer

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

Ovarian cancer has an unmet need for novel, alternate therapies.
Patients received a personalized vaccine developed from their own blood cells and tumor.

WASHINGTON, D.C. — A novel two-step immunotherapy approach yielded clinically beneficial responses in patients with advanced ovarian cancer, including one patient who achieved complete remission, according to data from two phase I clinical trials presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“This immunotherapeutic strategy has two steps — dendritic cell vaccination and adoptive T-cell therapy. This is the first time such a combination immunotherapy approach has been used for patients with ovarian cancer,” said Lana Kandalaft, Pharm.D., M.T.R., Ph.D., assistant professor and director of clinical development and operations at the Ovarian Cancer Research Center in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. “Most patients with ovarian cancer are diagnosed at an advanced stage and many of those relapse within two years; most die within five years. Given these grim outcomes, there is definitely a vast unmet need for the development of novel, alternate therapies.”

According to Kandalaft, the first step of the immunotherapy approach is to preserve the patient’s tumor at the time of surgery so it can be used to manufacture a personalized vaccine that teaches the patient’s own immune system to attack the tumor.

For this protocol, Kandalaft and colleagues isolated immune cells called dendritic cells from the blood of 31 patients with recurrent, progressive, stage 3 and 4 ovarian cancer. They then prepared the vaccine by exposing each patient’s dendritic cells to her own tumor tissue that had been collected during surgery. The first six patients were assigned to the first version of a vaccine while the other 25 were assigned to an enhanced vaccine with an optimized platform developed at the Penn Ovarian Cancer Research Center.

Nineteen of these patients showed clinical benefit after vaccine treatment and developed an antitumor immune response. Of these 19 patients, eight had no measurable disease at the end of the study and remained on maintenance vaccine therapy. One patient of the eight patients remained disease-free for 42 months following vaccine treatment.

Eleven patients who responded to the vaccine treatment but still had residual disease moved to the second step of the immunotherapy: adoptive T-cell therapy. At this point, the researchers removed immune cells called T cells from patients’ blood, stimulated and expanded the cells in the laboratory, and then reinjected them into the patients. The team found that because the T-cells had already been educated by the dendritic cell vaccine to attack the tumor cells, the adoptive T-cell transfer amplified the antitumor immune response. Of these 11 patients, seven had stable disease and one had a complete response.

While vaccination therapy alone showed about a 61 percent clinical benefit, the combination of both therapies showed about a 75 percent benefit, according to Kandalaft. “We offer patients with ovarian cancer a potential therapy with minor side effects and a good quality of life,” she said. The team continues to work to improve the vaccine platform to further enhance its efficacy.

Both treatments were given in conjunction with bevacizumab, a drug that controls blood vessel growth. Combining bevacizumab with immunotherapy makes a powerful duo, according to Kandalaft. Currently, the vaccine trial is still open to accrual to test new combinatorial strategies.

This study was funded by a National Cancer Institute Ovarian Specialized Program of Research Excellence grant, the National Institutes of Health and the Ovarian Cancer Immunotherapy Initiative.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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Jeremy.Moore@aacr.org
In Washington, D.C.,
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Biomarker Analysis Identified Women Most Likely to Benefit From T-DM1

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

Patients with the highest tumor HER2 levels benefited most.
The EMILIA phase III clinical trial led to FDA approval of T-DM1.
Presence of tumor PIK3CA mutations did not diminish treatment response.

WASHINGTON, D.C. — For women with metastatic, HER2-positive breast cancer, the amount of HER2 on their tumor might determine how much they benefit from a drug called trastuzumab emtansine (T-DM1), according to data from a subanalysis of the phase III clinical trial that led the U.S. Food and Drug Administration to approve the drug on Feb. 22, 2013. These findings were presented by José Baselga, M.D., Ph.D., physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York, N.Y., at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“EMILIA was a landmark phase III clinical trial,” said Baselga. “It showed that T-DM1 prolonged progression-free and overall survival for patients with HER2-positive metastatic breast cancer that had been previously treated with trastuzumab and a taxane chemotherapy compared with lapatinib plus capecitabine. Also, it provided proof-of-concept that a new class of drugs called antibody-drug conjugates can benefit patients.”

Antibody-drug conjugates consist of an antibody attached to a toxic chemotherapy, according to Baselga. In the case of T-DM1, the antibody is trastuzumab and the toxic chemotherapy is emtansine. Trastuzumab recognizes the protein HER2, which is found at high levels in HER2-positive breast cancers, and targets the emtansine to the HER2-positive cancer cells, which are killed by the toxic chemotherapy.

In this subanalysis, Baselga and colleagues analyzed tissue samples from patients enrolled in EMILIA to examine whether tumor levels of HER2, as assessed by the amount of HER2 messenger ribonucleic acid (mRNA), affected treatment response. Patients with tumor samples expressing greater than the median amount of tumor HER2 mRNA were considered to have high levels of HER2. Those with tumor samples expressing the median amount of tumor HER2 mRNA or less were considered to have low levels of HER2.

“Even though everyone enrolled in the clinical trial had breast cancer expressing elevated levels of HER2, we know that each person’s tumor has different molecular features,” said Baselga. “Even the degree to which HER2 expression is elevated differs from patient to patient.”

Consistent with the prior analysis, he and his colleagues found that all patients treated with T-DM1 had significantly longer progression-free and overall survival compared with those treated with lapatinib and capecitabine (9.6 months progression-free survival versus 6.4 months; and 30.9 months for overall survival versus 25.1 months).

Patients with tumors expressing higher levels of HER2 derived greater benefit from treatment with T-DM1 compared with patients with tumors expressing lower levels of HER2: Overall survival was 34.1 months for those with high levels of HER2 versus 26.5 months. For patients with tumors expressing higher levels of HER2, those receiving T-DM1 had a 47 percent decreased risk for death compared with those receiving lapatinib and capecitabine.

The researchers also investigated whether tumor mutations in the PIK3CA gene affected treatment response. According to Baselga, patients with PIK3CA-mutated, HER2-positive breast cancer normally do not respond as well to treatment with conventional HER2-targeted therapies such as trastuzumab compared with patients without PIK3CA mutations in their tumors.

However, for patients treated with T-DM1, PIK3CA mutation status did not significantly decrease progression-free survival.

“Our findings are an important step toward identifying the best therapy for individual patients with HER2-positive breast cancer,” said Baselga. “HER2-positive breast cancer is not a uniform disease; each patient is different. These data help us as we look to identify a panel of molecular features that we can use to make informed treatment decisions.”

Kadcyla (ado-trastuzumab emtansine or T-DM1) is a trademark of Genentech, a member of the Roche Group.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
April 6-10, 2013:
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Immunotherapy Showed Promising Antileukemia Activity in Pediatric Patients

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

Treatment used patients’ own immune cells.
After brief manipulation in the laboratory, cells were returned to patients.
Treatment was tolerated; three patients with ALL responded.

WASHINGTON, D.C. — Researchers using patients’ own immune cells in an immunotherapy approach called “anti-CD19 chimeric antigen receptor (CAR) T-cell therapy,” achieved responses in children whose acute lymphocytic leukemia (ALL) had returned after a bone marrow transplant, according to preliminary results presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“Anti-CD19 CAR T-cell therapy using patients’ own immune cells is a completely new way of treating childhood cancer,” said Daniel W. Lee, M.D., assistant clinical investigator in the Pediatric Oncology Branch of the National Cancer Institute. “It is not chemotherapy; therefore, it has a different side effect profile — we hope better tolerated. In the limited number of post-transplant patients we have treated so far, we’re getting acceptable toxicities, and we’re not seeing graft-versus-host disease.”

More than 95 percent of children initially diagnosed with ALL achieve remission, but a significant number of them relapse, according to Lee. Once they relapse, the prognosis is poor, with ALL accounting for the most deaths from cancer among children.

Other research teams are testing anti-CD19 CAR T-cell therapy in children with ALL that has returned after a bone marrow transplant, according to Lee. However, whether they are using immune cells from the transplant donor, or collecting and preparing the patient’s cells, the process is lengthy.

“Often these children with relapsed ALL don’t have that kind of time to wait,” Lee said. “We wanted something that could be done in a more timely manner. We decided to collect the immune cells, which are called T cells, directly from the patients, even though they’d had bone marrow transplants.”

The first three patients in the phase I trial had undergone a previous bone marrow transplant, although the trial is also open to patients who have never had a transplant. One patient had B-cell lymphoma and the other two had ALL.

The researchers collected T cells from the patients and modified them in the laboratory so that they would attach to a protein expressed by the leukemia cells, called CD19, and attack the cancers. The number of modified T cells, now called anti-CD19 CAR T cells, was expanded in the laboratory before they were returned to the patients.

The results so far indicate that this approach is a feasible and active treatment for pediatric patients with ALL, even those who relapse after a bone marrow transplant, according to Lee. One patient had a complete response and a second had a transient complete response, with minimal residual disease remaining. The lone lymphoma patient did not respond.

Cell expansion was robust. “We were able to get very good expansion — on average about 60-fold expansion of these cells during the 11-day culture period,” Lee said. “And we were able to insert the receptor, the anti-CD19 CAR, into those T cells with good efficiency.”

One patient did not produce a sufficient number of cells, which was likely related to recent intensive chemotherapy and resultant low T-cell count, according to Lee. Despite this, the few cells the patient did receive expanded dramatically and the patient temporarily achieved remission.

Lee and colleagues continue to test this approach in patients whose disease has returned after, or is refractory to, standard treatments whether or not they have had a bone marrow transplant.

“We think that the children who have never had a transplant might experience different toxicities,” said Lee. “Our first patient enrolled in this arm of the trial had never achieved disease remission after her initial diagnosis of ALL despite intensive chemotherapy. Strikingly, anti-CD19 CAR T-cell therapy resulted in the complete clearance of any detectable leukemia in this patient, and we were able to send her back to her primary oncologists for a bone marrow transplant.”

Lee’s research was partially funded by the St. Baldrick’s Foundation.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
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In Washington, D.C.,
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New Type of Experimental Drug Active in Platinum-resistant Ovarian Cancers

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

Women with highest expression of drug’s target protein benefited most.
If further confirmed, drug may represent new treatment option in ovarian cancer.
Future study will compare the drug to standard chemotherapy.

WASHINGTON, D.C. — The antibody-drug conjugate DMUC5754A, a novel member of a relatively new class of drugs, showed activity in women with ovarian cancer, even those with hard-to-treat, platinum-resistant disease, in a phase I trial presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10. Those women with the highest expression of the drug’s target, MUC16, gained the most benefit from treatment, which may help researchers predict which patients will benefit from treatment.

“If the activity of this drug is confirmed in additional trials, this will represent a novel type of therapy for ovarian cancer, with effectiveness in platinum-resistant ovarian cancer, which is the hardest type of ovarian cancer to treat,” said Joyce F. Liu, M.D., M.P.H., an instructor in medicine at Dana-Farber Cancer Institute and Harvard Medical School in Boston, Mass. “This would represent a real step forward in finding new, effective treatments for advanced ovarian cancer.”

According to Liu, ovarian cancer is the leading cause of death from gynecologic cancers in the United States. It affects more than 22,000 women per year and results in about 16,000 deaths per year. One of the biggest challenges in treating ovarian cancer is the development of platinum resistance, where the cancer cells stop responding to platinum chemotherapy, one of the most effective drugs in treating this cancer. Standard chemotherapies have limited effect against these platinum-resistant ovarian cancers, and women whose cancers have become platinum-resistant inevitably have disease progression.

“The drug we tested in this clinical trial, DMUC5754A, is from a new class of drugs called antibody-drug conjugates,” Liu said. “This drug consists of an antibody and a potent toxin joined by a cleavable linker. The antibody identifies a protein, MUC16, which is highly expressed in ovarian cancers, and targets the toxin to kill the cancer cells.”

Unlike other cancer treatments, the antibody-drug conjugate releases the toxin with relative selectivity to the MUC16-positive cancer cells. This allows delivery of drugs that would otherwise be too toxic for treatment, according to Liu.

She and her colleagues evaluated the safety, pharmacokinetics and pharmacodynamic activity of DMUC5754A in 44 patients with advanced, recurrent, platinum-resistant ovarian cancer. Researchers reported one complete response and four partial responses. All five of these confirmed responses occurred at the 2.4-mg/kg dose and in patients with high expression levels of MUC16 in their cancer cells.

During the study, two dose-limiting toxicities occurred: one grade 4 neutropenia and one grade 4 uric acid increase, which occurred at the maximum administered dose of 3.2 mg/kg. Grade 3 adverse events included fatigue in 9 percent of patients and neutropenia in 9 percent of patients. Fatigue was the most common adverse event at all dose levels and occurred in 57 percent of patients. Other commonly reported adverse events were nausea, vomiting, decreased appetite, diarrhea and peripheral neuropathy.

Liu and her colleagues next plan to evaluate this drug in comparison with standard chemotherapy.

DMUC5754A is being developed by Genentech, a member of the Roche Group.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
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Pezcoller Foundation and American Association for Cancer Research Honor Outstanding Achievements of Dr. Peter K. Vogt

registration@aacr.org () — Sat, 06 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — Peter K. Vogt, Ph.D., will receive the 2013 Pezcoller Foundation-AACR International Award for Cancer Research for his groundbreaking work on cancer-causing viruses that helped establish the field of cancer genetics.

Vogt, the executive vice president for scientific affairs and a professor at The Scripps Research Institute in La Jolla, Calif., will give an award lecture, “PI3K – from simplicity to complexity and back,” during the AACR Annual Meeting 2013 on Monday, April 8 at 5:30 p.m. ET in Ballroom A-B in the Walter E. Washington Convention Center, in Washington, D.C.

The Pezcoller Foundation-AACR International Award, now in its 16th year, recognizes an individual scientist of international renown who has made a major scientific discovery in basic or translational cancer research.

“Dr. Vogt is a preeminent scientist and we are very pleased to recognize his pioneering research on the genetic causes of cancer,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “His work with Rous sarcoma virus established the paradigm of oncogenes as potential inducers of cancer and had a profound impact on the field of cancer research.”

“I am greatly honored and delighted to be chosen as the 2013 recipient of the Pezcoller Foundation-AACR International Award for Cancer Research. I have long admired previous recipients of the Pezcoller Award and am both somewhat intimidated and greatly excited to be joining their ranks,” Vogt said.
Vogt has spent his entire career in cancer research, much of it focused on studying cancer-causing viruses. In 1970, he published his revolutionary work on the genetic basis of the cancer-causing capability of the Rous sarcoma virus. He subsequently made several further pioneering discoveries, including identifying several genes that are important in driving human cancers: myc, jun and PI3K. His more recent studies have shown that cancer-causing mutations in PI3K can render it a specific therapeutic target, and have led to the ongoing clinical development of numerous agents designed to exploit this.

Vogt received his doctorate from the University of Tübingen in Germany, and completed postdoctoral training at the University of California, Berkeley, before becoming associate professor of pathology at the University of Colorado School of Medicine in Denver. He then served as professor of microbiology at the University of Washington School of Medicine in Seattle, and then as the Hastings distinguished professor of microbiology and chairman of the Department of Microbiology at the University of Southern California School of Medicine in Los Angeles before going to The Scripps Research Institute.

Numerous accolades have been awarded to Vogt, including the California Scientist of the Year Award (1975), the Ernst Jung Prize for Medicine (1985), the Robert J. and Claire Pasarow Award (1987), the Bristol Myers Award (1989), the ICN International Prize in Virology (1989), the Charles S. Mott Prize from the General Motors Cancer Research Foundation (1991), the Gregor Johann Mendel Medal from the National Academy of the Sciences of the Czech Republic (2008) and the Albert Szent-Györgyi Prize for Progress in Cancer Research (2010).

Vogt is currently on the editorial boards of several journals, is on the board of directors of the Foundation for Advanced Cancer Studies and the scientific advisory board of the Sidney Kimmel Foundation for Cancer Research, and was elected to the American Academy of Microbiology Board of Governors (2009-2012). He is also a member of many academies and societies, including the AACR, the National Academy of Sciences, the German Academy of Sciences, the Institutes of Medicine and the American Association for the Advancement of Sciences, as well as being an honorary member of the Germany Society of Virology and the Society of Chinese Bioscientists in America.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
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Dr. Carlo M. Croce Honored With the 2013 AACR Princess Takamatsu Memorial Lectureship

registration@aacr.org () — Fri, 05 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) will honor Carlo M. Croce, M.D., professor and chair of the department of molecular virology, immunology and medical genetics and director of the Institute of Genetics at The Ohio State University School of Medicine in Columbus, with the seventh annual Princess Takamatsu Memorial Lectureship at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

Croce’s lecture, “Causes and Consequences of microRNA Dysregulation in Cancer,” will take place at 4:30 p.m. ET on Monday, April 8 in Ballroom C in the Walter E. Washington Convention Center.

Croce is being recognized for his research into the genetic mechanisms of cancer. He discovered numerous oncogenes and established the role of microRNAs in the development and progression of cancer.

The AACR Princess Takamatsu Memorial Lecture is presented to a scientist whose novel and significant work had or may have a far-reaching impact on the detection, diagnosis, treatment or prevention of cancer, and who embodies the dedication of the princess to multinational collaborations. Her Imperial Highness Princess Kikuko Takamatsu was instrumental in promoting cancer research and encouraging cancer scientists. She became a champion for these causes following her mother’s death from bowel cancer in 1933 at the young age of 43.

“I am extremely honored to receive this prestigious award. I knew the princess and attended several of the Takamatsu conferences,” said Croce, who served as chair of the Princess Takamatsu Symposia in 1996. “I am truly delighted and look forward to the AACR Annual Meeting.”

Croce started his quest to find cancer-causing genes by analyzing cancer-specific genomic abnormalities called chromosomal translocations. He began by studying the translocation that characterizes Burkitt’s lymphoma and showing that it led to the activation of the oncogene MYC. This finding was instrumental in determining that the chromosomal translocations observed in many human leukemias and lymphomas deregulate oncogenes, initiating the process of leukemia or lymphoma development.

Using cancer-specific chromosomal translocations as a starting point, Croce discovered numerous other cancer causing-genes, including BCL2, TCL1, ALL1/MLL1 and LZTS1. Using a similar approach, this time beginning with cancer-specific chromosomal deletion, he showed that microRNAs, which directly alter the expression of specific target genes, can be lost or gained in cancer cells.

Croce’s research led to the development of a microRNA gene expression chip to assess global expression of microRNAs in tissues and tumors. He found that specific microRNA signatures are associated with the diagnosis and prognosis of acute myeloid leukemia, chronic lymphocytic leukemia (CLL), multiple myeloma, lung cancer, colon cancer and other tumors and defined microRNAs that function as oncogenes or tumor suppressors. He found that the BCL2 gene that is responsible for follicular lymphoma is the target of the microRNAs miR-15 and miR-16; therefore, the loss of miR-15 and miR-16 leads to upregulation of BCL2 and contributes to the development of CLL.

By continuing to investigate CLL, Croce found that the microRNA miR-181b is a biomarker of disease progression. In addition, he found that the microRNA miR-155 is overexpressed in CLL and lung cancer, and that this may link inflammation and cancer. The clinical implication of Croce’s findings is that the development of drugs that reduce endogenous miR-155 levels may prevent or treat inflammation-related cancers.

In addition to being honored at the AACR Annual Meeting 2013 with the AACR Princess Takamatsu Memorial Lectureship, Croce is being inaugurated into the first class of the Fellows of the AACR Academy. In 1990, he received the AACR-Richard and Hinda Rosenthal Foundation Award, the AACR-Pezcoller International Award for Cancer Research in 1999 and the AACR G.H.A. Clowes Memorial Award in 2006. He also has served as a member of several AACR committees, as well as editor-in-chief of Cancer Research (1990-2000), a member of the board of directors (1990-1994) and chair of the 1998 AACR-Pezcoller International Award for Cancer Research Committee.

Croce has received numerous other accolades throughout his career, including two Outstanding Investigator Awards from the National Cancer Institute, the Raymond Bourgine Award and Gold Medal of Paris, an honorary doctorate in medicine from Uppsala University in Sweden, the Rod and Ceil Mortel Lecture in Cancer Research from Penn State University, the Italian Gold Medal for Public Health and the Gottleib Award from The University of Texas MD Anderson Cancer Center. He is also an elected member of the Institute of Medicine and the National Academy of Sciences, an honorary member of the Japanese Cancer Society and a foreign member of the Accademia Nazionale delle Scienze, delta dei XL in Italy.

Croce received his medical degree from the University of Rome La Sapienza in 1969. Throughout his career, he has held several positions and appointments in Philadelphia at the Wistar Institute, the University of Pennsylvania, the Children’s Hospital of Philadelphia, Temple University and Thomas Jefferson University, as well as at the National Institutes of Health.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
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AACR Honors Dr. Roger S. Lo With Outstanding Achievement in Cancer Research Award

registration@aacr.org () — Fri, 05 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) will recognize Roger S. Lo., M.D., Ph.D., of the University of California, Los Angeles (UCLA), with the 33rd Annual AACR Award for Outstanding Achievement in Cancer Research at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

Lo is assistant professor in the department of medicine, division of dermatology at the David Geffen School of Medicine at UCLA, with a joint appointment in the department of medical and molecular pharmacology, and a member of the Signal Transduction and Therapeutic Program at UCLA’s Jonsson Comprehensive Cancer Center.

Lo’s lecture, “How Melanoma Escapes From BRAF Inhibition,” will take place at 4 p.m. ET on Tuesday, April 9, in Ballroom C in the Walter E. Washington Convention Center.

“I am extremely honored to be recognized by the AACR and by this particular award, especially given the notable figures in cancer research who have previously received this award,” said Lo. “I accept it on behalf of my research team at UCLA and my collaborators and mentors. The support I have received from my family and wife has been absolutely critical. This award also acknowledges the sacrifices made by cancer patients in the search for greater knowledge.”

Since 1979, the AACR Award for Outstanding Achievement in Cancer Research has honored an investigator younger than 40 to recognize his or her meritorious achievements within the field of cancer research. Award recipients are nominated by their peers and are selected by the AACR International Selection Committee. Final determination is then made by the AACR’s Executive Committee.

Lo is being recognized for his seminal contributions to the understanding of how cancers escape from molecularly targeted therapies known as BRAF inhibitors. His research into how BRAF-mutant melanomas, which account for more than half of all cases of melanoma, adapt to BRAF inhibition is directly applicable to patient cancer: It has accelerated the clinical development of combination therapies designed to prevent this occurring and may be relevant to other cancers in addition to melanoma.

In 2008, after observing the striking first responses of patients with BRAF-mutant melanoma to the BRAF inhibitor vemurafenib, Lo began to work on understanding acquired resistance to BRAF inhibitor-based therapy before any patient had even relapsed. In addition to uncovering several molecular mechanisms by which BRAF-mutant melanomas escape the anticancer effects of BRAF inhibitors such as vemurafenib, he helped determine why the development of nonmelanoma squamous cell carcinoma is a side effect of these therapies.

Lo found that one of the most frequent ways in which melanomas become resistant to BRAF inhibitors is that they reactivate the MAPK signaling pathway and that MAPK pathway activation is commonly responsible for the development of nonmelanoma squamous cell carcinoma in patients being treated with BRAF inhibitors. These data provided the major scientific rationale for using a BRAF inhibitor in combination with an inhibitor of the MAPK pathway component MEK. Three phase III trials testing the combination of a BRAF inhibitor and a MEK inhibitor in patients with BRAF-mutant melanoma are currently under way. This combination therapy also appears to reduce the adverse events associated with treatment with just a BRAF inhibitor.

A second pathway Lo identified as responsible for melanomas escaping monotherapy with a BRAF inhibitor suggested that combining a BRAF inhibitor with either a PI3K inhibitor or an AKT inhibitor could be clinically effective. A clinical trial testing this idea using the BRAF inhibitor dabrafenib in combination with an AKT inhibitor has been designed and is in the early stages of implementation.

Lo received his medical degree from Cornell University Medical College in New York, N.Y., and his doctorate from the tri-institutional program at Cornell University Medical College, Rockefeller University and the Sloan-Kettering Institute. He completed an internship in medicine and a residency in dermatology at UCLA. Lo is also a Stand Up To Cancer 2011 Innovative Research Grant awardee and has been elected to the American Society for Clinical Investigation.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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AACR-ACS Award for Excellence in Cancer Epidemiology and Prevention to Honor Dr. Laurence N. Kolonel

registration@aacr.org () — Fri, 05 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) will recognize Laurence N. Kolonel, M.D., Ph.D., M.P.H., with the 22nd AACR-American Cancer Society Award for Excellence in Cancer Epidemiology and Prevention at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

The AACR-American Cancer Society Award for Research Excellence in Cancer Epidemiology and Prevention was established in 1992 to honor outstanding research accomplishments in the fields of cancer epidemiology, biomarkers and prevention. Kolonel will give his lecture, “Advancing Epidemiologic Research: Studies in ‘Special’ Populations,” on Tuesday, April 9, at 3 p.m. ET in Ballroom A-B in the Walter E. Washington Convention Center.

Kolonel was professor in the Cancer Epidemiology Program at the University of Hawaii Cancer Center and a professor of public health at the John A. Burns School of Medicine at the University of Hawaii, in Honolulu.

Kolonel began his career studying ethnicity and cancer among Japanese immigrants and other ethnic groups in Hawaii in the 1970s and was one of the first to establish a cancer registry that included ethnic and racial minorities in the United States. As a pioneer in the study of the etiology of cancer, Kolonel is recognized for his work on the ethnic and racial disparities of cancer, as well as his research on the role of diet and lifestyle in cancer causation. His studies were critical in establishing that diet and lifestyle modifications had enormous potential to prevent cancer. Kolonel’s work has resulted in more than 450 original, peer-reviewed articles.

One of Kolonel’s most notable achievements was his leadership in establishing a multiethnic cohort of more than 200,000 participants, primarily individuals of African-American, Japanese, Latino, Native Hawaiian and Caucasian origin. In addition, biological specimens were obtained from approximately 70,000 of the cohort participants to form a unique biorepository of blood and urine samples. Analysis of data obtained from the cohort has already led to many important cancer discoveries, including the identification of a genetic variation linked to risk for prostate cancer, especially among men of African-American origin. Ongoing and future studies are expected to clarify the risk factors associated with different cancer risks among the five predominant ethnicities represented in the cohort.
Kolonel graduated from Williams College, in Williamstown, Mass., with a degree in chemistry and earned his medical degree from Harvard Medical School, in Boston, Mass. Kolonel received a master’s degree in public health and doctorate in epidemiology from the University of California, Berkeley. In addition, he served as a major in the U.S. Air Force from 1972 to 1974.

Throughout his distinguished career, Kolonel has received many honors, including the MERIT Award from the National Cancer Institute (NCI) in 2002, in recognition of his Multiethnic Cohort Study. He received a Regents Medal for Excellence in Research at the University of Hawaii in 2003 and was named the 2005 “Scientist of the Year” by the Honolulu chapter of the Achievement Rewards for College Scientists Foundation. In addition, Kolonel was a visiting scholar at the Division of Cancer Epidemiology and Genetics at the NCI and is a former associate editor of the AACR journals Cancer Research and Cancer Epidemiology, Biomarkers & Prevention.

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Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
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Dr. Fadlo R. Khuri Receives 2013 AACR-Richard and Hinda Rosenthal Memorial Award

registration@aacr.org () — Fri, 05 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) will honor Fadlo R. Khuri, M.D., with the 37th Annual AACR-Richard and Hinda Rosenthal Memorial Award during the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10. Khuri, deputy director of the Winship Cancer Institute of Emory University School of Medicine in Atlanta, Ga., is receiving this award in recognition of his accomplishments as an investigator in lung and aerodigestive medical oncology.

His award lecture, “Targeting Survival Signaling in Aerodigestive Cancers,” will take place at 10 a.m. ET on Wednesday, April 10, in Ballroom C in the Walter E. Washington Convention Center.

“As a practicing clinical oncologist and as a physician-scientist, it is a profound honor for me to receive the AACR-Richard and Hinda Rosenthal Memorial Award, particularly in light of the extraordinary role models who have previously received this award,” said Khuri, who is also professor and chair of hematology and medical oncology, adjunct professor of medicine, pharmacology and otolaryngology, and Roberto C. Goizueta distinguished chair in translational cancer research at Emory University School of Medicine. “The award recognizes work by our team of physicians and scientists, at Emory University’s Winship Cancer Institute and The University of Texas MD Anderson Cancer Center, all of which was carried out with the sole purpose of making a difference for patients with lung and head and neck cancers.”

This award provides incentive to young investigators early in their careers. It was established in 1977 by the AACR and the Rosenthal Family Foundation to recognize research that has made, or promises to make, a notable contribution to improved care of people with cancer.

One of Khuri’s early accomplishments is the recognition of the potential of oncolytic viral therapy in cancer treatment. ONYX-015 is an adenovirus that selectively replicates in p53-deficient cancer cells and is, therefore, capable of selectively destroying those cancer cells. Khuri recognized the limitation of standard chemotherapy in cancers with a mutated tumor suppressor p53, and so he combined ONYX-015 with chemotherapy in a controlled clinical trial and demonstrated superior disease control in patients with recurrent head and neck cancer, a disease that recurs rapidly with either therapy alone. ONYX-015 was the first viral anticancer agent approved in Asia.

He demonstrated that the expression of retinoic acid receptor and COX-2 indicate poor prognosis in lung cancer, and identified prognostic factors such as DAPK methylation and lack of IL-10 expression that independently predict cancer-specific survival. These studies have added further knowledge to individualized adjuvant therapy. He also showed that farnesyl transferase inhibitors can reverse the resistance of non-small cell lung cancers to taxanes.

Khuri’s studies toward development of novel cancer agents led to the hypothesis of pharmacologically-enhanced oncogene addiction, which describes the use of anticancer agents to enhance the dependency of cancer cells to certain pathways so that the addiction can be exploited for effective treatment strategies. Based on this phenomenon, Khuri and colleagues discovered that despite mTOR suppression, rapamycin induces the paradoxical up-regulation of Akt. These studies may lead to the development of new oncogenic pathway-targeting agents for cancer treatment. These and other contributions of Khuri toward testing of novel treatment strategies in clinical trials led to his recognition internationally in the fields of chemoprevention and chemotherapy.

He was instrumental in obtaining the National Cancer Institute (NCI) designation to Winship Cancer Institute in 2009. Additionally, he worked to increase NCI peer-reviewed funding in cancer at Emory, from $7.4 million in 2000 to more than $30 million in 2011. His contributions to cancer research and patient care extend beyond the laboratory. He increased patient enrollment in therapeutic clinical trials at Emory from 143 in 2001 to more than 500 in each of the last three years.

Khuri currently serves on the editorial board of the AACR’s journal, Cancer Prevention Research, and is the editor-in-chief of Cancer, a journal of the American Cancer Society. He is an elected member of the American Society of Clinical Investigation. Additionally, he has received the American Cancer Society Clinical Oncology Career Development Award, the Georgia Cancer Coalition Distinguished Clinical Scholar Award and the Middle East Medical Assembly’s Naji Sahyoun Memorial Award.

Khuri received his medical degree from Columbia University College of Physicians and Surgeons in New York, N.Y., in 1989. He completed his internship and residency at the Boston City Hospital, Boston University School of Medicine, in Massachusetts in 1990 and 1992, respectively, and a fellowship at the New England Medical Center at Tufts University School of Medicine in Boston in 1995.

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Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
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Research Team Recognized for Advancing Pancreatic Cancer Research Through Innovative, Collaborative Science

registration@aacr.org () — Fri, 05 Apr 2013 12:00:00 GMT

The AACR’s Seventh Annual Team Science Award honors researchers from Johns Hopkins, Emory and Memorial Sloan-Kettering Cancer Center

WASHINGTON, D.C. — The Pancreatic Cancer Sequencing Team in the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins University will receive the Seventh Annual AACR Team Science Award during the American Association for Cancer Research’s Annual Meeting 2013, held in Washington, D.C., April 6-10.

The AACR Team Science Award recognizes an outstanding interdisciplinary research team for its innovative and meritorious scientific work that has advanced or will likely advance cancer research, detection, diagnosis, prevention or treatment. This multi-institutional team was selected based on its tremendous impact on understanding of the fundamental genetic changes that characterize pancreatic cancer. This research has immediate clinical implications. The award will be presented during the opening ceremony on Sunday, April 7, at 8:15 a.m. ET in Ballroom A-B in the Walter E. Washington Convention Center.

“On behalf of the AACR, I congratulate this outstanding team,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “Their research has greatly contributed to our knowledge of pancreatic cancer, which currently has an extremely poor prognosis. They have provided a wonderful example of the innovative scientific discoveries we can expect to find when the efforts of multiple institutions and different biomedical fields collaborate.”

The interdisciplinary team, led by Ralph H. Hruban, M.D., comprises 20 faculty members from three different institutions: Johns Hopkins University in Baltimore, Md.; Emory University in Atlanta, Ga.; and Memorial Sloan-Kettering Cancer Center in New York, N.Y.

“This is a talented group of scientists with a shared goal — alleviating the suffering caused by pancreatic cancer,” said Hruban, professor of pathology and oncology at Johns Hopkins University. “When we came together as a team, the synergy was electric. It has been both tremendous fun and enormously productive.”

Working together for more than 10 years, the team obtained specimens of various pancreatic cancer types from more than 250 patients. They sequenced the exomes of ductal adenocarcinomas and neuroendocrine tumors of the pancreas, and their research led to the discovery of a new cancer pathway, DAXX/ATRX mutations and alternative lengthening of telomeres, and the identification of new familial pancreatic cancer genes, PALB2 and ATM. In addition, they defined the time course for pancreatic neoplasia development and found a unique mutation profile for each of the four cystic tumors of the pancreas. These discoveries have provided important insight into the disease, and have important clinical applications. A clinical test was developed to screen for PALB2 mutations in patients with a family history of pancreatic cancer. The team is currently developing a gene-based test to determine pancreatic cyst type.

“To make progress against a disease as difficult as pancreatic cancer, investigators with diverse expertise are essential. We have been very fortunate to have a large number of investigators, tops in their field, on our team, selflessly giving their time and effort to the cause,” said team member Bert Vogelstein, M.D., Clayton professor of oncology and pathology at Johns Hopkins University.

The team’s contributions have resulted in two papers in the Proceedings in the National Academy of Sciences, four publications in Science and manuscripts in Nature, Science Translational Medicine and AACR journals Cancer Discovery, Clinical Cancer Research and Cancer Research.

The AACR Team Science Award, generously supported by grants from Eli Lilly and Company, is presented with the intent to stimulate change within the traditional cancer research culture by recognizing those individuals and institutions that value and foster interdisciplinary team science. The winning team collectively receives a $50,000 prize and is recognized for its scientific accomplishments and leadership role in fostering team science to advance cancer research.

Honorees are (in alphabetical order):

N. Volkan Adsay, M.D., professor of pathology at Emory University;
Peter Allen, M.D., surgical oncologist at Memorial Sloan-Kettering Cancer Center;
Michael Choti, M.D., professor of surgery and oncology; chief of the Division of Surgical Oncology; Jacob C. Handelsman endowed chair of abdominal surgery and professor in the Whiting School of Engineering Center for Computer Integrated Surgical Systems at Johns Hopkins University;
Luis Diaz, M.D., associate professor of oncology at Johns Hopkins University;
James Eshleman, M.D., Ph.D., professor in the departments of pathology and oncology, associate director of the Molecular Diagnostics Laboratory at Johns Hopkins University;
Michael Goggins, M.D., professor of pathology, medicine and oncology at Johns Hopkins University;
Joseph Herman, M.D., associate professor of radiation oncology and molecular radiation sciences at Johns Hopkins University;
Ralph H. Hruban, M.D., professor of pathology and oncology; director, Division of Gastrointestinal/Liver Pathology; director, Sol Goldman Pancreatic Cancer Research Center; and deputy director for research of the Department of Pathology at Johns Hopkins University;
Christine Iacobuzio-Donahue, M.D., professor of pathology, oncology and surgery and head of the Rapid Medical Donation Program at Johns Hopkins University;
Scott Kern, M.D., professor of oncology and pathology at Johns Hopkins University;
Kenneth Kinzler, Ph.D., professor of oncology at Johns Hopkins University;
Alison Klein, Ph.D., associate professor of oncology, pathology and epidemiology and head of the National Familial Pancreas Tumor Registry at Johns Hopkins University;
David S. Klimstra, M.D., professor of pathology at Memorial Sloan-Kettering Cancer Center;
Anirban Maitra, M.B.B.S., professor of pathology and oncology at Johns Hopkins University;
Alan Meeker, Ph.D., assistant professor of pathology, urology and oncology at Johns Hopkins University;
Nick Papadopoulos, Ph.D., professor of oncology at Johns Hopkins University;
Victor Velculescu, M.D., Ph.D., professor of oncology at Johns Hopkins University;
Bert Vogelstein, M.D., Clayton professor of oncology and pathology at Johns Hopkins University, co-director of the Ludwig Center at Johns Hopkins and Howard Hughes Medical Institution investigator;
Christopher Wolfgang, M.D., Ph.D., associate professor of surgery at Johns Hopkins University; and
Laura Wood, M.D., Ph.D., assistant in pathology at Johns Hopkins University.

Major funding for the Pancreatic Cancer Sequencing Team in the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins University was provided by The Lustgarten Foundation for Pancreatic Cancer Research, the Sol Goldman Center for Pancreatic Cancer Research, the Caring for Carcinoid Foundation, the Michael Rolfe Foundation and the National Institutes of Health.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
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In Washington, D.C.,
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Dr. Alexander Levitzki Awarded Seventh Annual AACR Award for Outstanding Achievement in Chemistry in Cancer Research

registration@aacr.org () — Fri, 05 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) will recognize Alexander Levitzki, Ph.D., for his contributions to signal transduction therapy and his work on the development of tyrosine kinase inhibitors as effective agents against cancer with the 2013 AACR Award for Outstanding Achievement in Chemistry in Cancer Research at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

Levitzki is a professor in the Department of Biological Chemistry at Hebrew University of Jerusalem, in Israel. His lecture, “Eradicating Tumors by Targeting Nonviral Vectors Carrying PolyIC,” will take place at 3 p.m. ET on Tuesday, April 9, in Ballroom A-B of the Walter E. Washington Convention Center.

Levitzki pioneered the development of tyrosine phosphorylation inhibitors (tyrphostins) against a wide spectrum of protein tyrosine kinases. In 1988, he conducted a systematic screening of low molecular weight protein tyrosine kinase inhibitors synthesized by his team, and identified the most potent compounds that inhibited the EGF-dependent proliferation of cancer cells. He demonstrated the activity and specificity of these inhibitors at a time when most researchers believed they could not be developed for clinical applications, since such an inhibitor may have extensive inhibitory activity against other members of the kinase “super-family” and, therefore, lack any specificity. Levitzki subsequently synthesized inhibitors that showed remarkable specificity to several other kinase targets including HER2, the Bcr-Abl fusion protein, the PDGF receptor, the VEGF receptor and Jak2.

Levitzki’s concept of targeted cancer therapy using protein tyrosine kinase inhibitors is extensively used by the pharmaceutical industry worldwide to develop anticancer drugs. His studies formed the basis for the development of drugs like imatinib, crizotinib and lapatinib, used for the treatment of patients with chronic myeloid leukemia, lung cancer and breast cancer, respectively. Currently there are more than 200 such inhibitors at various stages of the U.S. Food and Drug Administration’s approval process.

His method of large-scale screening of synthetic compounds tested against a large spectrum of protein kinases for specificity, followed by systematic testing in cell lines and animal studies, became the standard procedure in most of the laboratories working in that field.

Levitzki’s team developed pharmacophores, describing the structural features that are requisites for the binding of synthetic compounds to their respective targets, in order to trigger a biological response. The chemical principles he summarized and published in Science in 1995 have become the reference for the field of kinase inhibitors.

Levitzki has received numerous awards throughout his impressive career, including the Israel Prize in Biochemistry, the Wolf Prize for Medicine, the Hamilton-Fairley Award from the European Society of Medical Oncology, the Rothschild Prize in Biology and two Prostate Cancer Foundation Research Awards. Last year he received the Nauta Award in Pharmacochemistry, which is the highest award from the European Federation for Medicinal Chemistry. He is a member of the board of governors of the Israel Cancer Association, was chairman of the Division of Natural Sciences at the Israel Academy of Sciences, an honorary member of the American Society of Biological Chemists and an elected member of the European Molecular Biology Organization. He served as president and vice president of the Federation of Israeli Societies of Experimental Biology and received a doctor honoris causa degree from Ben-Gurion University in Beersheva, Israel. Levitzki was a member of the scientific advisory board of Teva Pharmaceutical Industries Ltd. and has served on the editorial board of several journals, including the Journal of Biological Chemistry, Science, European Journal of Biochemistry, Current Signal Transduction Therapy and the European Journal of Chemical Biology.

Levitzki received his doctorate in biophysics and biochemistry from the Hebrew University of Jerusalem and the Weizmann Institute of Science in Rehovoth, Israel. He completed a postdoctoral fellowship in the department of biochemistry at the University of California, Berkeley.

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Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

AACR Honors 30 Women in Cancer Research Scholars

registration@aacr.org () — Thu, 04 Apr 2013 12:00:00 GMT

WASHINGTON, D.C. — The American Association for Cancer Research (AACR) is honoring 30 Women in Cancer Research scholars at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10. This award, now in its sixth year, enhances the education and training of female researchers and increases their visibility and recognition in the field of cancer research.

This annual award provides funds for the participation of early-career, meritorious scientists. Scholars are selected on the basis of their qualifications, references from mentors and an estimation of the potential professional benefit to the awardees. By attending the meeting, awardees are able to build networks, attend important scientific sessions, receive feedback on their research and gain many more benefits of attendance. Since its inception in 2008, more than 85 scientists have been awarded funds to support their attendance at the AACR Annual Meeting.

Merck Oncology and the William H. Prusoff Foundation have generously provided support to fund the participation of young investigators to attend this year’s Annual Meeting. Since 2011, these two organizations have provided more than $60,000 in funding.

The names and affiliations of the 2013 Women in Cancer Research Scholars, along with the numbers and titles of their presentations can be found online at www.aacr.org/wicr.

AACR-Women in Cancer Research (WICR) is a group within the AACR. It is open to all AACR members, male and female. WICR is dedicated to achieving full participation of women in cancer research by recognizing their scientific achievements and fostering their career development and advancement in cancer research through all stages of their careers.

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Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.,
April 6-10, 2013:
(202) 249-4005

AACR CEO Dr. Margaret Foti Receives the Distinguished Partner in Hope Award

registration@aacr.org () — Thu, 04 Apr 2013 12:00:00 GMT

PHILADELPHIA — Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the American Association for Cancer Research, was honored with the Distinguished Partner in Hope Award during the Annual Colorectal Cancer Conference hosted by the Abramson Cancer Center of the University of Pennsylvania in Philadelphia on March 22. Foti was recognized for her outstanding contribution to cancer research, prevention and therapy.

She delivered the keynote lecture, “Progress Against Cancer in the New Era of Cancer Science and Medicine,” at the conference, which was attended by more than 500 cancer survivors.

“I am deeply honored to receive this special recognition from the Abramson Cancer Center,” said Foti. “It is important to disseminate information about recent scientific advances in cancer research and treatment to cancer patients and the public. I have the highest regard for the outstanding work of the center and its division of gastroenterology, and I applaud the Abramson Cancer Center for its educational commitment.”

The Abramson Cancer Center hosts informative, day-long educational conferences on many specific types of cancer. The only conferences of their kind in the region, they serve as an interactive forum where cancer patients, survivors and families can learn about the latest advances in prevention, treatment and research and actively engage with the Cancer Center’s expert faculty and staff. The Colorectal Cancer Conference, held at the Hilton Philadelphia City Avenue, has separate tracks during the meeting that address specific issues relating to pancreatic, colon, esophageal and stomach cancers.

At each conference, an award is presented to an individual or organization to recognize the difference they have made in cancer awareness, research or patient care in our community and beyond. This year the Cancer Center recognized Foti for her work in the field.

“Dr. Foti leads a remarkable organization that has not only catalyzed cancer research, but the AACR has also played a pivotal role in making translational research a high-priority reality,” said Chi Van Dang, M.D., Ph.D., director of the Abramson Cancer Center. “Her limitless dedication is clearly reflected by her outstanding leadership of the AACR, which has become a shining light and a beacon of hope for cancer patients. In this regard, we are honored that she accepts the Distinguished Partner in Hope Award from the Abramson Cancer Center.”

In addition to this honorable achievement, Foti has received many other accolades for her contributions to cancer research and advocacy. Most recently in October 2012, she received the Founders Award for Excellence in Cancer Research during a special recognition ceremony at the National Brain Tumor Society 2012 Summit in Boston, Mass. Last year she was recognized as a First Lady of the Intercultural Cancer Council and she also received the 2012 Biotech Humanitarian Award from the Biotechnology Industry Organization. She was also awarded Research!America’s 2012 Raymond and Beverly Sackler Award for Sustained National Leadership.

In 2010, Foti received the first Margaret Foti Award, which was established in cooperation with the University of Catania Ph.D. Oncology Program and the Italian League Against Cancer of Catania. In 2009, she received the first Margaret Kripke Legend Award from The University of Texas MD Anderson Cancer Center, the European CanCer Organization Lifetime Achievement Award and a citation from Philadelphia Mayor Michael Nutter for her dedication to increasing awareness of the importance of cancer research, as well as for her pivotal role in designating May as National Cancer Research Month. Foti was also the first recipient of an AACR award created in her name in 2007 for leadership and extraordinary achievements in cancer research. Her numerous other awards and recognitions for work in the United States and abroad include honorary memberships in the Japanese Cancer Association, the European Association for Cancer Research and the Hungarian Cancer Society, as well as three honorary doctorates in medicine and surgery.

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Follow the AACR on Twitter: @aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

About the Abramson Cancer Center
The Abramson Cancer Center of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute since 1973, one of 40 such Centers in the United States. The Abramson Cancer Center is dedicated to innovative and compassionate cancer care. The clinical program, comprised of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient care coordinators, currently sees over 90,000 outpatient visits, over 11,800 inpatient discharges, and provides over 37,000 chemotherapy treatments, and more than 66,000 radiation treatments. Not only is the Abramson Cancer Center dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the Abramson Cancer Center is home to the 400+ basic, translational and clinical scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty are committed to improving the prevention, diagnosis and treatment of cancer. To learn more visit www.penncancer.org.

Media Contact:
Lauren Riley
(215) 446-7155
lauren.riley@aacr.org

AACR Welcomes New Members to the Board of Directors and Nominating Committee

registration@aacr.org () — Thu, 04 Apr 2013 12:00:00 GMT

PHILADELPHIA — The members of the American Association for Cancer Research will welcome Carlos L. Arteaga, M.D., as president-elect 2013-2014 on Tuesday, April 9, at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

Arteaga is professor of medicine and cancer biology at Vanderbilt University School of Medicine where he holds the Donna S. Hall chair in breast cancer research. He serves as associate director for clinical research and director of the Breast Cancer Research Program of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. He will begin serving his one-year term as AACR president in April 2014.

“Dr. Arteaga is an internationally recognized leader in translational and clinical research,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “His extraordinary expertise in these areas will be a tremendous asset to the AACR as we continue to seek innovative new ways to accelerate the translation of pioneering research discoveries into improvements in patient care. We are delighted to welcome him on board as the new president-elect.”

In his vision statement, Arteaga vowed to leverage the resources of the AACR to increase and sustain funding of multidisciplinary, multi-investigator, basic science-based translational and clinical research in cancer. Further, he will make it a priority to promote and retain young laboratory-based investigators and physician-scientists in cancer research.

In addition, the members have elected five distinguished scientists to serve on the AACR Board of Directors for the 2013-2016 term: Mary C. Beckerle, Ph.D.; Michael A. Caligiuri, M.D.; Hans Clevers, M.D., Ph.D.,; Elizabeth M. Jaffee, M.D.; and Victor E. Velculescu, M.D., Ph.D.

Mary C. Beckerle, Ph.D., is chief executive officer and director of the Huntsman Cancer Institute at the University of Utah in Salt Lake City. She is also associate vice president for cancer affairs, distinguished professor of biology and adjunct professor of oncological sciences at the University of Utah.

Beckerle is currently a member of the AACR Science Policy and Government Affairs Committee and served as a scientific lecturer at the Meet-the-Expert Session, “Genesis and Impact of Cytoskeletal Changes in Transformed Cells,” at the AACR Annual Meeting 2011.

Michael A. Caligiuri, M.D., is chief executive officer of the James Cancer Hospital and Solove Research Institute at The Ohio State University in Columbus, Ohio. He is also director of The Ohio State University Comprehensive Cancer Center; vice president for health sciences, cancer programs; chair in cancer research at the John L. Marakas Nationwide Insurance Enterprise Foundation; and professor in the departments of molecular virology, immunology, medical genetics and internal medicine at Ohio State University.

Caligiuri is currently chairperson of the AACR Publications Committee and a member of the Council of Scientific Advisors, the Science Policy and Government Affairs Committee, the Clinical and Translational Cancer Research Committee and the steering committee for the Cancer Immunology Working Group. He was also chairperson for the Annual Meeting Program Committee in 2009 and a member of the editorial boards of Molecular Cancer Therapeutics and Clinical Cancer Research.

Hans Clevers, M.D., Ph.D., is president of The Royal Netherlands Academy of Arts and Sciences in Amsterdam and professor in molecular genetics at the Academic Biomedical Center at the University of Utrecht, in Utrecht, Netherlands.

Clevers has served on several AACR selection committees including the AACR-Princess Takamatsu Memorial Lectureship Selection Committee, the Landon Basic Prize Selection Committee and the Laboratory Research Awards Selection Committee. He was also on the editorial board of Molecular Cancer Research.

Elizabeth M. Jaffee, M.D., is a professor of oncology and pathology at Johns Hopkins University School of Medicine in Baltimore, Md., active staff in oncology at Johns Hopkins Hospital, associate director for translational research and co-director of the Gastrointestinal Cancers Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. She is also medical director of the Johns Hopkins Oncology Center Cell Processing and Gene Therapy Facility, deputy director of the Institute for Translational and Clinical Research and on the faculty of the graduate programs in immunology, cellular and molecular medicine, and pharmacology at the Johns Hopkins University School of Medicine.

Jaffee is currently chairperson of the AACR Cancer Immunology Working Group and a member of the Tumor Microenvironment Working Group and the Science Policy and Government Affairs Committee. She has served as co-chairperson of Mentored Grants and Research Fellowships and of the special conferences, “Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances” and “Tumor Immunology: Basic and Clinical Advances.” She was also an associate editor of Cancer Research and member of the editorial boards of Clinical Cancer Research and Molecular Cancer Therapeutics.

Victor E. Velculescu, M.D., Ph.D., is professor of oncology at Johns Hopkins University School of Medicine, co-director of the Cancer Biology Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and director of cancer genetics at the Ludwig Center for Cancer Genetics and Therapeutics at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

Velculescu is chairperson of the AACR Basic Cancer Research Grants Scientific Review Committee and a member of the Education and Training Committee. Additionally, he was a member of the Annual Meeting 2012 Program Committee, the Breast Cancer Research Foundation-AACR Grants for Translational Breast Cancer Scientific Review Committee and was a keynote speaker at the 2007 International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

On Tuesday, April 9, at 7 a.m. ET, during the AACR Annual Meeting Business Meeting, the AACR leadership will induct Charles L. Sawyers, M.D., as president of the AACR.

Sawyers is chair of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center in New York, N.Y., and a Howard Hughes Medical Institute investigator. He is also a professor in the Cell and Developmental Biology Program at the Joan and Sanford I. Weill Graduate School of Medical Sciences of Cornell University. He is co-leader of the Stand Up To Cancer-Prostate Cancer Foundation Prostate Cancer Dream Team: Precision Therapy of Advanced Prostate Cancer, and is scientific editor of Cancer Discovery.

Sawyers will succeed Frank McCormick, Ph.D., F.R.S., D.Sc. (hon.), director of the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center. McCormick holds the E. Dixon Heise distinguished professorship in oncology and the David A. Wood distinguished professorship of tumor biology and cancer research at UCSF. Additionally, he is the associate dean of the UCSF School of Medicine and a distinguished professor in residence in the department of microbiology and immunology as well as in the department of biochemistry and biophysics.

McCormick served with distinction as AACR president for the 2012-2013 term and will assume the role of past-president (2013-2014).

In addition, the following renowned scientists have been elected to serve as members of the Nominating Committee for the 2013-2015 term: Elizabeth H. Blackburn, Ph.D.; Kenneth W. Kinzler, Ph.D.; Scott W. Lowe, Ph.D.; and Martine J. Piccart, M.D., Ph.D.

Elizabeth Blackburn, Ph.D., is the Morris Herzstein Professor of Biology and Physiology in the departments of biochemistry and biophysics, and microbiology and immunology at the University of California, San Francisco.

Blackburn, recipient of the 2009 Nobel Prize in Physiology or Medicine, is currently scientific editor of Cancer Discovery, deputy editor of Cancer Prevention Research and a member of the Stand Up To Cancer Scientific Advisory Committee, the AACR Cancer Prevention Committee and the Science Policy and Government Affairs Committee. Blackburn has also served as AACR president from 2010 to 2011, chairperson of the Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research Selection Committee, co-chairperson of the AACR Cancer Progress Report 2011 Writing Committee, keynote speaker at the 2010 AACR International Conference on Frontiers in Cancer Prevention Research and chairperson of the AACR Award for Lifetime Achievement in Cancer Research Committee. She was also on the board of directors (2006-2009) and a senior editor of Molecular Cancer Research.

In addition, Blackburn will be inaugurated into the first class of the Fellows of the AACR Academy during the Annual Meeting.

Kenneth W. Kinzler, Ph.D., is director of the Ludwig Center for Cancer Genetics and Therapeutics at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and professor of oncology at Johns Hopkins University School of Medicine.

He is currently a member of the Fight Colorectal Cancer-AACR Award Selection Committee and the Publications Committee. Kinzler has served as chairperson of the Editor-in-Chief Search Committee for Molecular Cancer Research and the AACR Laboratory Research Awards Selection Committee. He was also a member of the board of directors (2008-2011).

Scott W. Lowe, Ph.D., is an investigator at the Howard Hughes Medical Institute, member of Memorial Sloan-Kettering Cancer Center and chair of the Geoffrey Beene Cancer Research Center at Memorial Sloan-Kettering Cancer Center in New York, NY. He is also adjunct associate professor in the Department of Physiology and Biophysics at Stony Brook University School of Medicine in Stony Brook, N.Y. and an adjunct professor at Cold Spring Harbor Laboratory, in Cold Spring Harbor, N.Y.

Lowe is chairperson of the AACR International Conference on Frontiers in Basic Cancer Research 2013. He was a co-committee member and keynote speaker at the 2011 AACR-Japanese Cancer Association joint conference, “The Latest Advances in Liver Cancer Research: From Basic Science to Therapeutics,” chairperson of AACR Laboratory Research Awards Selection Committee, chairperson of the special conference, “Mouse Models of Cancer” and a member of the board of directors (2005-2008).

Martine J. Piccart, M.D., Ph.D., is a professor of oncology at the Université Libre de Bruxelles in Brussels, Belgium, and head of the medicine department at the Institut Jules Bordet in Brussels. She is president-elect and a board member of the European CanCer Organization and president of the European Society for Medical Oncology.

Piccart is a member of the AACR-Women in Cancer Research Council. She was co-chairperson of the 2010 Annual Meeting Education Committee, the 2010 AACR Dead Sea International Conference on Advances in Cancer Research: From the Laboratory to the Clinic, and the 2004 and 2010 Annual Meeting Program Committees.

In addition, Piccart will be inaugurated into the first class of the Fellows of the AACR Academy during the Annual Meeting.

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Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.:
April 6-10, 2013
(202) 249-4005

Cisplatin-resistant Cancer Cells Sensitive to Experimental Anticancer Drugs Called PARP Inhibitors

registration@aacr.org () — Wed, 03 Apr 2013 12:00:00 GMT

Cisplatin-resistant non-small cell lung cancer cells expressed high levels of hyperactivated PARP1.
Cells succumbed to PARP inhibitors in vitro.
PARP inhibitor slowed cisplatin-resistant tumor growth in mice.

PHILADELPHIA — Poly (ADP-ribose) polymerase inhibitors may be a novel treatment strategy for patients with cancer that has become resistant to the commonly used chemotherapy drug cisplatin, according to data from a preclinical study published in Cancer Research, a journal of the American Association for Cancer Research.

“Cisplatin is one of the most widely used conventional, anticancer chemotherapy drugs,” said Guido Kroemer, M.D., Ph.D., professor at University Paris Descartes in Paris, France. “Unfortunately, most patients respond only transiently to cisplatin therapy because their cancer cells develop ways to resist the effects of the drug.”

Kroemer and colleagues set out to identify the biochemical changes that arise as cancer cells become resistant to cisplatin in the hope that the information could provide clues to potential new therapies. They focused their study on non-small cell lung cancer (NSCLC) cells because NSCLC is the leading cause of cancer-related morbidity and mortality worldwide and patients with NSCLC are frequently treated with cisplatin, according to Kroemer.

The researchers found that most NSCLC cell lines resistant to cisplatin had high levels of the protein poly (ADP-ribose) polymerase 1 (PARP1) and elevated amounts of poly (ADP-ribosyl) (PAR). In addition, they found that the PARP1 was hyperactivated. They observed similar results for cisplatin-resistant mesothelioma, ovarian cancer and cervical cancer cell lines.

When cisplatin-resistant NSCLC cell lines with high levels of hyperactivated PARP1 and PAR were exposed to each of two distinct PARP inhibitors, the cell lines initiated a cellular process that resulted in their death. Levels of PAR were more predictive of response to PARP inhibitors than were levels of PARP1 itself, suggesting that PAR may be an effective biomarker of response to cisplatin, according to Kroemer.

He and his colleagues then examined whether treatment with a PARP inhibitor affected the growth of tumors in mice xenografted with human NSCLC cell lines. They found that treatment significantly slowed tumor growth.

“Our data show that in most cases, cisplatin resistance is linked to stereotyped biochemical changes in cancer cells that render them vulnerable to PARP inhibitors,” said Kroemer. “This has clear implications for new treatment regimens and for developing biomarkers of response to cisplatin. We are following up these exciting clinical possibilities in our laboratory.”

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New Metabolite-based Diagnostic Test Could Help Detect Pancreatic Cancer Early

registration@aacr.org () — Fri, 29 Mar 2013 12:00:00 GMT

Test requires measurement of certain metabolite levels in patients’ blood.
Diagnostic test showed high sensitivity and specificity.

PHILADELPHIA — A new diagnostic test that uses a scientific technique known as metabolomic analysis may be a safe and easy screening method that could improve the prognosis of patients with pancreatic cancer through earlier detection.

Researchers examined the utility of metabolomic analysis as a diagnostic method for pancreatic cancer and then validated the new approach, according to study results published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Although surgical resection can be a curative treatment for pancreatic cancer, more than 80 percent of patients with pancreatic cancer have a locally advanced or metastatic tumor that is unresectable at the time of detection,” said Masaru Yoshida, M.D., Ph.D., associate professor and chief of the Division of Metabolomics Research at Kobe University Graduate School of Medicine in Kobe, Japan. “Conventional examinations using blood, imaging and endoscopy are not appropriate for pancreatic cancer screening and early detection, so a novel screening and diagnostic method for pancreatic cancer is urgently required.”

Using gas chromatography mass spectrometry, the researchers measured the levels of metabolites in the blood of patients with pancreatic cancer, patients with chronic pancreatitis and healthy volunteers. They randomly assigned 43 patients with pancreatic cancer and 42 healthy volunteers to a training set and 42 patients with pancreatic cancer and 41 healthy volunteers to a validation set. They included all 23 patients with chronic pancreatitis in the validation set.

Analysis of the metabolomic data generated from the training set indicated that levels of 18 metabolites were significantly different in the blood of patients with pancreatic cancer compared with the healthy volunteers. Further investigation led the researchers to develop a method to predict a pancreatic cancer diagnosis using assessment of the levels of just four metabolites. In the training set, the approach demonstrated 86 percent sensitivity and 88.1 percent specificity. When tested again in the validation set, which included patients with chronic pancreatitis, the method demonstrated 71.4 percent sensitivity and 78.1 percent specificity.

“Our diagnostic approach using serum metabolomics possessed higher accuracy than conventional tumor markers, especially at detecting the patients with pancreatic cancer in the cohort that included the patients with chronic pancreatitis,” Yoshida said. “This novel diagnostic approach, which is safe and easy to apply as a screening method, is expected to improve the prognosis of patients with pancreatic cancer by detecting their cancers early, when still in a resectable and curable state.”

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Number of Cancer Survivors Expected to Increase to 18 Million by 2022

registration@aacr.org () — Wed, 27 Mar 2013 12:00:00 GMT

The current number of cancer survivors is 13.7 million.
The increase is primarily due to aging of the population.
Survival is not uniform across cancer types.

WASHINGTON, D.C. — The American Association for Cancer Research released its second Annual Report on Cancer Survivorship in the United States in advance of the AACR Annual Meeting 2013, which will be held in Washington, D.C., April 6-10.

The report, published in the AACR’s journal Cancer Epidemiology, Biomarkers & Prevention, shows that as of January 2012, there were approximately 13.7 million cancer survivors in the United States, a number that is expected to rise by 31 percent to 18 million by 2022.

“The increase in the number of survivors will be due primarily to an aging of the population. By 2020, we expect that two-thirds of cancer survivors are going to be age 65 or older,” said Julia Rowland, Ph.D., director of the Office of Cancer Survivorship at the National Cancer Institute, a part of the National Institutes of Health (NIH).

The current report was based on an analysis of the Surveillance, Epidemiology and End Results Program and population projections from the U.S. Census Bureau, both government-funded databases.

In addition to providing estimates of future cancer survival trends, the report shows that survival is not uniform across cancer subtypes. Currently, women with breast cancer account for 22 percent of survivors, while men with prostate cancer make up 20 percent. People with lung cancer, the second most common cancer in terms of diagnosis, only represent 3 percent of survivors.

“For patients with prostate cancer, we have a nearly 100 percent five-year survival rate, and breast cancer has made tremendous strides as well, with five-year survival rising from 75 percent in 1975 to almost 89 percent in 2012,” said Rowland. “However, we clearly need to have better diagnostic tools and better treatments for lung cancer.”

According to Rowland, the increase in the cancer survivor population will present new challenges for the health care community. Patients diagnosed with cancer will likely have comorbid conditions that need to be managed, and Rowland estimates 16 percent will have had a previous malignancy.

“How to ensure that these patients lead not only long lives, but healthy and productive lives, will be a vital challenge to all of us,” said Rowland.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

AACR Elects Carlos L. Arteaga, M.D., as President-elect 2013-2014

registration@aacr.org () — Wed, 27 Mar 2013 12:00:00 GMT

PHILADELPHIA — The members of the American Association for Cancer Research have elected Carlos L. Arteaga, M.D., as their president-elect for 2013-2014. Arteaga is a professor of medicine and cancer biology at Vanderbilt University School of Medicine where he holds the Donna S. Hall chair in breast cancer research. He also serves as associate director for clinical research and director of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

In his new role, Arteaga will work collaboratively with the AACR Board of Directors and the 34,000-plus membership to further the AACR’s mission to prevent and cure cancer through research, education, communication and collaboration. He will officially become president-elect on Tuesday, April 9, at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10, and will assume the presidency in April 2014.

“I am very grateful to the AACR and its members for this honor and opportunity,” said Arteaga. “I look forward to working with the association and meaningfully contributing to its leadership role and progress in the fight against cancer in these difficult but also exciting times.”

“Dr. Arteaga’s contributions to breast cancer research have had a major impact on the lives of breast cancer patients,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “We are thrilled that an esteemed expert in translational and clinical research has been elected to serve as the next AACR president-elect. Dr. Arteaga shares in the AACR’s mission to prevent and cure cancer, and we know that he will lead the association with much vigor and commitment to ensure that we continue to accelerate progress against this insidious disease.”

Arteaga’s involvement in the AACR spans more than a decade. He was a member of the Board of Directors (2004-2007); chair of the AACR Special Conferences Committee (2002-2008); member of the Annual Meeting Program Committee in 2012 and 2013; co-chairperson of the “Molecularly Targeted Therapies: Mechanisms of Resistance” special conference in 2012; member of the Clinical and Translational Cancer Research Grants Scientific Review Committee in 2012; member of the AACR Outstanding Investigator Award for Breast Cancer Research Selection Committee in 2011; co-chairperson of the AACR-Japanese Cancer Association joint conference; co-chair of the AACR special conference “Advances in Breast Cancer Research” in 2003, 2005, 2007, 2009 and 2013; and an editorial board member of the AACR’s journal, Molecular Cancer Therapeutics, from 2002 to 2012.

Arteaga was also an editorial board member of Clinical Cancer Research from 2001 to 2004 and is currently deputy editor. He has served on behalf of the AACR as co-chair of the annual CTRC–AACR San Antonio Breast Cancer Symposium since 2009 and is a principal investigator on the Stand Up To Cancer Dream Team, “Targeting the PI3K Pathways in Women’s Cancers.”

His research interests include oncogene signaling and molecular therapeutics in breast cancer with an emphasis on targeted therapies, mechanisms of drug resistance, translational research and investigator-initiated clinical trials. Early in his career, Arteaga was the first to report the role of IGF-I receptors and TGF beta on breast cancer progression and their potential as therapeutic targets. More recent work has focused on the role of presurgical and neoadjuvant trials to discover molecular biomarkers that inform patient selection in clinical trials and/or for the discovery of mechanisms of drug resistance in breast cancer. He showed the role of aberrant activation of the PI3K pathway in promoting escape from antiestrogens and the ability of inhibitors of HER2 and PI3K to reverse resistance to antiestrogen therapy in human breast cancer in studies focused on hormone receptor-positive breast cancer. All of his work has significant implications for novel clinical trials in patients with breast cancer, some of which are completed or in progress.

He has received many honors and awards, including the AACR-Richard and Hinda Rosenthal Award, the American Cancer Society Clinical Research Professor Award, the Gianni Bonadonna Award from the American Society of Clinical Oncology, the Brinker Award for Scientific Distinction from the Susan G. Komen for the Cure Breast Cancer Foundation and, early in his career, the Clinical Investigator Award from the U.S. Department of Veteran Affairs. Additionally, he is an elected member of the Association of American Physicians and the American Society for Clinical Investigation and a member of Susan G. Komen’s Scientific Advisory Board.

Arteaga received his medical degree in 1980 from the Facultad de Ciencias Médicas at the Universidad de Guayaquil in Ecuador. Following internal medicine residency at Emory University in Atlanta, Ga., Arteaga completed a fellowship in medical oncology at The University of Texas Health Science Center at San Antonio. He joined the faculty at Vanderbilt University in 1989.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org
In Washington, D.C.:
April 6-10, 2013
(202) 249-4005

Ganetespib Demonstrates Potency Against ALK-positive Lung Cancer and Overcomes Crizotinib Resistance

registration@aacr.org () — Tue, 26 Mar 2013 12:00:00 GMT

Ganetespib killed ALK-driven NSCLC cell lines more effectively than crizotinib.
Displayed greater antitumor activity and prolonged survival in a mouse model.
Potential as a new option for treating ALK-dependent lung cancers.

PHILADELPHIA — A drug that indirectly impairs the function of several cancer-driving proteins, including anaplastic lymphoma kinase, may be an effective new treatment for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer.

The drug, ganetespib, may also be effective for treating patients who have become resistant to the only FDA-approved targeted therapy for this disease, crizotinib, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

“Lung cancer, a leading cause of death, is no longer thought of as a single disease, but rather as a group of diseases, each with a distinct genetic profile,” according to David Proia, Ph.D., associate director of cancer biology at Synta Pharmaceuticals Corporation, the company that funded the research. “This realization has paved the way for the design of new treatments tailored to the specific biological characteristics of a patient’s tumor.

“For example, patients with lung cancer caused by alterations in the anaplastic lymphoma kinase (ALK) protein typically respond well to crizotinib, which blocks that activity of the modified ALK and consequently kills off the cancer cells,” said Proia. “However, as is the case for many cancer drugs, most patients treated with crizotinib eventually become resistant to the drug.”

Proia and colleagues investigated ganetespib as an alternative treatment for ALK-positive non-small cell lung cancer (NSCLC). Ganetespib targets heat shock protein 90 (Hsp90), a chaperone for many different proteins, including ALK, to ensure proper functioning. When Hsp90 is blocked, ALK can no longer work properly and is destroyed by the cell. Once ALK is lost, the cancer cells die and the tumors shrink.

Ganetespib had 30 times greater potency than crizotinib against a cultured ALK-positive NSCLC cell line, resulting in the complete loss of ALK protein expression. In addition, the drug was active against ALK-positive lung cancer cell lines that had become resistant to the effects of crizotinib.

The researchers then compared ganetespib and crizotinib in mice xenografted with human ALK-positive NSCLC cancer cells. Ganetespib displayed greater antitumor activity and prolonged animal survival as compared to crizotinib. It was also shown that ganetespib had meaningful activity in a patient with ALK-driven NSCLC who had responded to, and then progressed, following crizotinib therapy.

“Ganetespib therapy represents a new option for treating ALK-dependent lung cancer in sequence with direct ALK inhibitors and/or for treating patients who relapse following direct ALK inhibitor therapy,” said Proia.

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Early-onset Baldness in African-American Men May Be Linked to Prostate Cancer

registration@aacr.org () — Tue, 26 Mar 2013 12:00:00 GMT

African-American men are at high risk for developing prostate cancer.
Bald African-American men younger than 60 years of age were at greatest risk.
Frontal balding increased risk of severe disease.

PHILADELPHIA — Baldness was associated with an increased risk of prostate cancer among African-American men, and risk for advanced prostate cancer increased with younger age and type of baldness, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“We focused on African-American men because they are at high risk for developing prostate cancer and are more than twice as likely to die from prostate cancer than other groups in the United States,” said Charnita Zeigler-Johnson, Ph.D., research assistant professor at the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania in Philadelphia. “Although this is a high-risk group for poor prostate cancer outcomes, no published study had focused on evaluating baldness as a potential risk factor in a sample of African-American men.”

Zeigler-Johnson and her colleagues identified 318 men with prostate cancer and 219 controls among participants who enrolled in the Study of Clinical Outcomes, Risk and Ethnicity (SCORE) between 1998 and 2010. All of them were African-American and had varying degrees of baldness. They obtained information on type of baldness (none, frontal and vertex) and other medical history using a questionnaire.

The researchers found that any baldness was associated with a 69 percent increased risk of prostate cancer. In particular, African-American men with frontal baldness, and not vertex baldness, were more than twice as likely to have been diagnosed with advanced prostate cancer. This association was even stronger among men who were diagnosed when younger than 60, with a sixfold increase in high-stage prostate cancer and a fourfold increase in high-grade prostate cancer.

In addition, among younger men with prostate cancer, those with frontal baldness were more likely to have a high prostate-specific antigen level at diagnosis.

“Early-onset baldness may be a risk factor for early-onset prostate cancer in African-American men, particularly younger men,” said Zeigler-Johnson. “Pending future studies to confirm our results, there is a potential to use early-onset baldness as a clinical indicator of increased risk for prostate cancer in some populations of men.”

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American Association for Cancer Research to Inaugurate the First Class of the Fellows of the AACR Academy

registration@aacr.org () — Mon, 25 Mar 2013 12:00:00 GMT

PHILADELPHIA — The American Association for Cancer Research will inaugurate the first class of the Fellows of the AACR Academy at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

The AACR Academy has been created to recognize and honor distinguished scientists whose major scientific contributions have propelled significant innovation and progress against cancer. These Fellows have been selected through a rigorous peer review process that evaluates individuals on the basis of their stellar scientific achievements in cancer research.

“Our Board of Directors made the decision to establish the AACR Academy as a mechanism for recognizing scientists whose contributions to the cancer field have had an extraordinary impact. Membership in the Fellows of the AACR Academy will be the most prestigious honor bestowed by the American Association for Cancer Research,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR.

The Fellows of the AACR Academy is a separate entity within the American Association for Cancer Research, and only individuals who have made exceptional contributions to cancer and/or cancer-related biomedical science are eligible for election.

The inaugural class of Fellows will be inducted into the AACR Academy on Friday, April 5, at the National Museum of Women in the Arts in Washington, D.C., at 6:30 p.m. Reporters who wish to attend this dinner must RSVP to Jeremy Moore, associate director of media relations at the AACR, at jeremy.moore@aacr.org no later than March 28.

The induction ceremony will be followed by a meeting of the Academy on Saturday, April 6, and special recognition of the inaugural Fellows during the opening plenary session on Sunday, April 7. These events will be annual occurrences at future AACR Annual Meetings.

The inaugural class of Fellows of the AACR Academy will consist of 106 individuals, symbolizing the age of the organization upon establishment of the Academy.

Future classes of Fellows shall consist of no more than 11 individuals, in honor of the 11 founding members of the American Association for Cancer Research. These Fellows will be elected by a vote of all the Fellows of the AACR Academy.

The inaugural Fellows of the AACR Academy are:

Karen H. Antman, M.D., John Sandson Professor of Health Sciences; Dean, Boston University School of Medicine; Provost, Boston University Medical Campus
David Baltimore, Ph.D., Robert Andrews Millikan Professor of Biology, President Emeritus, California Institute of Technology
Françoise Barré-Sinoussi, Ph.D., Professor and Director, Regulation of Retroviral Infections Unit, Virology Department, Institut Pasteur
Paul Berg, Ph.D., Cahill Professor of Biochemistry, Emeritus, Stanford University School of Medicine
Joseph R. Bertino, M.D., American Cancer Society Professor; Chief Scientific Officer, The Cancer Institute of New Jersey; University Professor of Medicine & Pharmacology, UMDNJ-RWJMS; Interim Director, The Stem Cell Institute of N.J.
J. Michael Bishop, M.D., Professor, Department of Microbiology and Immunology; Director, G. W. Hooper Research Foundation; Chancellor Emeritus, University of California, San Francisco
Mina J. Bissell, Ph.D., Distinguished Scientist, Life Sciences Division, Lawrence Berkeley National Laboratory
Elizabeth H. Blackburn, Ph.D., Morris Herzstein Endowed Chair in Biology and Physiology and Professor, Departments of Biochemistry/Biophysics and Microbiology/Immunology, University of California, San Francisco
Sydney Brenner, MB.BCh., D.Phil., Founder, Acidophil, LLC; Senior Distinguished Fellow of the Crick-Jacobs Center, Salk Institute for Biological Studies
Angela H. Brodie, Ph.D., Professor of Pharmacology, University of Maryland School of Medicine; Investigator, University of Maryland Marlene and Stewart Greenebaum Cancer Center
Mario R. Capecchi, Ph.D., Distinguished Professor, Human Genetics and Biology, University of Utah School of Medicine; Investigator, Howard Hughes Medical Institute
Webster K. Cavenee, Ph.D., Director, Ludwig Institute for Cancer Research; Distinguished Professor, University of California, San Diego
Martin Chalfie, Ph.D., William R. Kenan, Jr. Professor of Biological Sciences, Department of Biological Sciences, Columbia University
Zhu Chen, M.D., Ph.D., Vice-Chairman, 12th Standing Committee of the National People’s Congress; Chairman, 15th Chinese Peasants and Workers Democratic Party, Central Committee
Aaron J. Ciechanover, M.D., D.Sc., Distinguished Research Professor, Technion-Israel Institute of Technology
Bayard D. Clarkson, M.D., Member and Head, Laboratory of Hematopoietic Cell Kinetics, Memorial Sloan-Kettering Cancer Center
Donald S. Coffey, Ph.D., Catherine Iola and J. Smith Michael Distinguished Professor of Urology, Johns Hopkins University School of Medicine
Stanley N. Cohen, M.D., Kwoh-Ting Li Professor in the School of Medicine, Professor of Genetics, and Professor of Medicine, Stanford University
Suzanne Cory, Ph.D., Honorary Distinguished Professorial Fellow, Molecular Genetics of Cancer Division, Walter and Eliza Hall Institute of Medical Research and Vice-Chancellor’s Fellow, University of Melbourne
Carlo M. Croce, M.D., Professor and Chair, Department of Molecular Virology, Immunology and Medical Genetics; Director, Institute of Genetics, The Ohio State University School of Medicine
Tom Curran, Ph.D., Deputy Scientific Director, Division of Cancer Pathobiology; Mai and Harry F. West Chair in Pediatric Research, The Children's Hospital of Philadelphia Research Institute; Professor of Pathology and Laboratory Medicine, Cell and Developmental Biology, Perelman School of Medicine; Associate Director, Translational Genomics, University of Pennsylvania
Brian J. Druker, M.D., Director, Knight Cancer Institute, Oregon Health and Science University; JELD-WEN Chair of Leukemia Research; Investigator, Howard Hughes Medical Institute
Raymond N. DuBois, M.D., Ph.D., Executive Director, The Biodesign Institute; Dalton Chair, School of Health Solutions, Arizona State University
Sir Martin J. Evans, Ph.D., Chancellor, Cardiff University
Emmanuel Farber, M.D., Ph.D., Chairman Emeritus and Professor, Department of Pathology, University of Toronto
Napoleone Ferrara, M.D., Distinguished Professor of Pathology, Senior Deputy Director for Basic Sciences, Moores Cancer Center, University of California, San Diego
Isaiah J. Fidler, D.V.M., Ph.D., Professor, Department of Cancer Biology, R.E. "Bob" Smith Distinguished Chair in Cell Biology, Head, Cancer Metastasis Laboratory, The University of Texas MD Anderson Cancer Center
Bernard Fisher, M.D., Distinguished Service Professor, Department of Surgery, University of Pittsburgh
Joseph F. Fraumeni Jr., M.D., Senior Investigator and Advisor, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Emil Frei III, M.D., Physician-in-Chief Emeritus, Richard and Susan Smith Distinguished Professor of Medicine Emeritus, Dana-Farber Cancer Institute, Harvard Medical School
Elaine V. Fuchs, Ph.D., Rebecca C. Lancefield Professor, Laboratory of Mammalian Cell Biology and Development, Rockefeller University; Investigator, Howard Hughes Medical Institute
Judy E. Garber, M.D., M.P.H., Director, Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute; Professor of Medicine, Harvard Medical School
Walter Gilbert, Ph.D., Carl M. Loeb University Professor Emeritus, Department of Molecular and Cellular Biology, Harvard University
Alfred G. Gilman, M.D., Ph.D., Regental Professor of Pharmacology Emeritus, University of Texas Southwestern Medical Center
Carol W. Greider, Ph.D., Daniel Nathans Professor and Director, Department of Molecular Biology and Genetics; Professor of Oncology, Johns Hopkins University School of Medicine
Roger C. L. Guillemin, M.D., Ph.D., Distinguished Professor, Salk Institute for Biological Studies
Sir John B. Gurdon, D.Phil., Distinguished Group Leader, Wellcome Trust/Cancer Research U.K. Gurdon Institute
William N. Hait, M.D., Ph.D., Global Head at Janssen Research and Development, LLC
Leland H. Hartwell, Ph.D., Virginia G. Piper Chair of Personalized Medicine, Chief Scientist, Center for Sustainable Health, Biodesign Institute, Arizona State University; President Emeritus, Fred Hutchinson Cancer Research Center
Avram Hershko, M.D., Ph.D., Distinguished Professor at the Rappaport Faculty of Medicine, Technion-Israel Institute of Technology; Adjunct Professor of Pathology, New York University School of Medicine
James F. Holland, M.D., Distinguished Professor of Neoplastic Diseases, Mount Sinai Medical Center
Jimmie C. Holland, M.D., Wayne E. Chapman Chair in Psychiatric Oncology; Attending Psychiatrist, Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center
Waun Ki Hong, M.D., Vice Provost, Clinical Research; Head, Division of Cancer Medicine; Samsung Distinguished University Chair in Cancer Medicine, The University of Texas MD Anderson Cancer Center
Leroy E. Hood, M.D., Ph.D., President and Co-founder, Institute for Systems Biology; Full Member, University of Washington Molecular and Cellular Biology Program; Professor at Large, Keck Graduate Institute of Applied Life Sciences
H. Robert Horvitz, Ph.D., David H. Koch Professor of Biology, Massachusetts Institute of Technology; Member, MIT Koch Institute for Integrative Cancer Research; Member, MIT McGovern Institute for Brain Research; Investigator, Howard Hughes Medical Institute
Susan Band Horwitz, Ph.D., Distinguished Professor, Rose C. Falkenstein Chair in Cancer Research, Associate Director for Therapeutics, Albert Einstein Cancer Center; Co-Chair, Department of Molecular Pharmacology, Albert Einstein College of Medicine
Sir R. Timothy Hunt, Ph.D., Emeritus Group Leader, Clare Hall Laboratories, Cancer Research U.K.
Tony Hunter, Ph.D., Director, Salk Institute Cancer Center; American Cancer Society Professor of Molecular and Cell Biology, Renato Dulbecco Chair, The Salk Institute for Biological Studies
Tyler Jacks, Ph.D., Director, David H. Koch Institute for Integrative Cancer Research; Professor of Biology, Massachusetts Institute of Technology; Investigator, Howard Hughes Medical Institute
Peter A. Jones, Ph.D., D.Sc., Distinguished Professor of Urology and Biochemistry & Molecular Biology; Mark A, J. Ruth, and Stillman F. Sawyer Chair in Cancer Research, University of Southern California (USC) Norris Comprehensive Cancer Center
V. Craig Jordan, Ph.D., D.Sc., Professor of Oncology and Pharmacology, Vincent T. Lombardi Chair of Translational Cancer Research, Vice Chair, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University
Yuet Wai Kan, M.D., Louis K. Diamond Professor of Hematology, Departments of Laboratory Medicine and Medicine, University of California, San Francisco
Mary-Claire King, Ph.D., American Cancer Society Professor, Departments of Medicine and Genome Sciences, University of Washington
Eva Klein, M.D., Ph.D., Professor Emeritus, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
George Klein, M.D., Ph.D., Professor Emeritus, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
Alfred G. Knudson Jr., M.D., Ph.D., Distinguished Scientist and Senior Advisor to the President, Fox Chase Cancer Center
Brian K. Kobilka, M.D., Professor, Molecular and Cellular Physiology and Medicine, Stanford University School of Medicine
Margaret L. Kripke, Ph.D., Chief Scientific Officer of the Cancer Prevention and Research Institute of Texas; Vivian L. Smith Distinguished Chair in Immunology Emerita and Professor Emerita, Department of Immunology, and Professor Emerita, Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center
Philip Leder, M.D., Professor Emeritus, Department of Genetics, Harvard Medical School
Robert J. Lefkowitz, M.D., Investigator, Howard Hughes Medical Institute; James B. Duke Professor of Medicine; Professor of Biochemistry and Chemistry, Duke University Medical Center
Arnold J. Levine, Ph.D., Professor, Simons Center for Systems Biology, Institute for Advanced Study; Professor, Cancer Institute of New Jersey
Lawrence A. Loeb, M.D., Ph.D., Professor of Pathology, Biochemistry and Director, Joseph Goldstein Memorial Cancer Research Laboratory, University of Washington School of Medicine
Tak W. Mak, Ph.D., Director, Advanced Medical Discovery Institute and Director, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Princess Margaret Cancer Centre; Professor, Departments of Medical Biophysics and Immunology, University of Toronto
Lynn M. Matrisian, Ph.D., Vice President, Scientific and Medical Affairs, Pancreatic Cancer Action Network
Frank McCormick, Ph.D., Director, Helen Diller Family Comprehensive Cancer Center; Associate Dean, School of Medicine, University of California, San Francisco
John Mendelsohn, M.D., Director, Sheik Kalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy and Past President, MD Anderson Cancer Center
Donald Metcalf, M.D., Professor Emeritus, University of Melbourne; Carden Fellow in Cancer Research, Division of Cancer and Hematology, the Walter and Eliza Hall Institute of Medical Research
Enrico Mihich, M.D., Presidential Scholar and Special Assistant to the President for Sponsored Research, Dana-Farber Cancer Institute
Beatrice Mintz, Ph.D., Professor and Jack Schultz Chair in Basic Research, Fox Chase Cancer Center
Luc Montagnier, M.D., Co-Founder and President, World Foundation for AIDS Research and Prevention; Director of Research Emeritus, Centre National de la Recherché Scientifique; Professor Emeritus, Pasteur Institute
Harold L. Moses, M.D., Hortense B. Ingram Professor of Molecular Oncology; Professor of Cancer Biology, Medicine and Pathology; Director Emeritus, Vanderbilt-Ingram Comprehensive Cancer Center
Sir Paul M. Nurse, Ph.D., Director, Francis Crick Institute, London; President, The Royal Society
Olufunmilayo I. Olopade, M.D., Walter L. Palmer Distinguished Service Professor of Medicine & Human Genetics; Associate Dean for Global Health; Director, Center for Clinical Cancer Genetics, University of Chicago Pritzker School of Medicine
Arthur B. Pardee, Ph.D., Professor of Biological Chemistry and Molecular Pharmacology Emeritus, Harvard Medical School
Martine J. Piccart, M.D., Ph.D., Professor of Oncology, Université Libre de Bruxelles; Director of Medicine, Jules Bordet Institute
Sir Bruce A. J. Ponder, MB.BChir., Ph.D., Founding Director, Cancer Research U.K. Cambridge Research Institute; Professor and Head of Oncology, University of Cambridge; Honorary Consultant Physician, Cambridge University Hospitals
Sir Richard J. Roberts, Ph.D., Chief Scientific Officer, New England Biolabs, Inc.
Irwin A. Rose, Ph.D., Distinguished Professor Emeritus, Department of Physiology and Biophysics, University of California, Irvine
Janet D. Rowley, M.D., Blum-Riese Distinguished Professor of Medicine, Molecular Genetics and Cell Biology, and Human Genetics, University of Chicago
Frederick Sanger, Ph.D., Emeritus Professor, Laboratory for Molecular Biology, University of Cambridge
Alan C. Sartorelli, Ph.D., Alfred Gilman Professor of Pharmacology, Yale University School of Medicine
Andrew V. Schally, Ph.D., Distinguished Medical Research Scientist; Head, Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, Department of Veterans Affairs; Distinguished Leonard M. Miller Professor of Pathology, Miller School of Medicine, University of Miami
Phillip A. Sharp, Ph.D., Institute Professor and Faculty Member, David H. Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology
Charles J. Sherr, M.D., Ph.D., Herrick Foundation Chair, Department of Tumor Cell Biology, St. Jude Children’s Research Hospital; Investigator, Howard Hughes Medical Institute
Osamu Shimomura, Ph.D., Distinguished Scientist, Marine Biological Laboratory; Professor of Physiology Emeritus, Boston University School of Medicine
Dennis J. Slamon, M.D., Ph.D., Director, Clinical/Translational Research; Director, Revlon/UCLA Women’s Cancer Research Program, Jonsson Comprehensive Cancer Center; Professor of Medicine; Chief of the Division of Hematology/Oncology; Executive Vice Chair for Research, David Geffen School of Medicine, University of California, Los Angeles
Oliver Smithies, D.Phil., Weatherspoon Eminent Distinguished Professor, University of North Carolina School of Medicine at Chapel Hill
Michael B. Sporn, M.D., Professor of Pharmacology and Medicine, Geisel School of Medicine at Dartmouth
Louise C. Strong, M.D., Sue and Radcliffe Killam Chair, Department of Genetics, and Professor, Department of Genetics, The University of Texas MD Anderson Cancer Center
Takashi Sugimura, M.D., President, Toho University; President Emeritus, National Cancer Center
Sir John E. Sulston, Ph.D., Professor and Chair of the Institute for Science, Ethics and Innovation, University of Manchester
Jack W. Szostak, Ph.D., Investigator, Howard Hughes Medical Institute; Professor of Genetics, Harvard Medical School; Professor of Chemistry and Chemical Biology, Harvard University; Alexander Rick Distinguished Investigator, Department of Molecular Biology, Massachusetts General Hospital
Roger Y. Tsien, Ph.D., Professor of Pharmacology, Chemistry and Biochemistry, University of California, San Diego; Investigator, Howard Hughes Medical Institute
Arthur C. Upton, M.D., Emeritus Professor of Environmental Medicine and Clinical Professor of Environmental and Community Medicine, University of Medicine and Dentistry, Robert Wood Johnson Medical School
George F. Vande Woude, Ph.D., Distinguished Scientific Fellow, Van Andel Research Institute
Bert Vogelstein, M.D., Clayton Professor of Oncology and Pathology, Howard Hughes Medical Institute Investigator, Director of the Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Comprehensive Cancer Center
Peter K. Vogt, Ph.D., Executive Vice President for Scientific Affairs; Professor, Department of Molecular and Experimental Medicine; The Scripps Research Institute
Daniel D. Von Hoff, M.D., Physician in Chief, Distinguished Professor, Translational Genomics Research Institute; Professor of Medicine, Mayo Clinic; Chief Scientific Officer, Scottsdale Health Care; Professor, University of Arizona College of Pharmacy
Geoffrey M. Wahl, Ph.D., Professor, Gene Expression Laboratory; Daniel and Martina Lewis Chair, Salk Institute for Biological Studies
James D. Watson, Ph.D., Chancellor Emeritus, Cold Spring Harbor Laboratory
Lee W. Wattenberg, M.D., Professor of Laboratory Medicine and Pathology Emeritus, Masonic Cancer Center, University of Minnesota
Robert A. Weinberg, Ph.D., Member, Whitehead Institute for Biomedical Research; Professor, Department of Biology, Massachusetts Institute of Technology; Director, Ludwig/MIT Center for Molecular Oncology
John H. Weisburger, Ph.D., Research Professor of Pathology, Graduate School of Basic Medical Sciences, New York Medical College
Jane Cooke Wright, M.D., Deceased (1919 – 2013)
Shinya Yamanaka, M.D., Ph.D., Director and Professor, Center for iPS Cell Research and Application, Kyoto University; Senior Investigator, Gladstone Institute of Cardiovascular Disease; and Professor of Anatomy, University of California, San Francisco
Harald zur Hausen, M.D., Professor Emeritus, German Cancer Research Center

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Functional Characteristics of Antitumor T Cells Change With Increasing Time After Therapeutic Transfer

registration@aacr.org () — Thu, 21 Mar 2013 12:00:00 GMT

Beneficial effect of genetically engineered antitumor T cells was transient.
Functionality of T cells changed over time.
Strategies are needed to sustain antitumor functionality.

PHILADELPHIA — Scientists have characterized how the functionality of genetically engineered T cells administered therapeutically to patients with melanoma changed over time. The data, which are published in Cancer Discovery, a journal of the American Association for Cancer Research, highlight the need for new strategies to sustain antitumor T cell functionality to increase the effectiveness of this immunotherapeutic approach.

Early clinical research has indicated that cell-based immunotherapies for cancer, in particular melanoma, have potential because patients treated with antitumor T cells frequently have an initial tumor response; however, those responses are often transient.

“The cell-based immunotherapy we utilized was that of genetically engineered T cells,” said James R. Heath, Ph.D., Elizabeth W. Gilloon Professor of Chemistry at the California Institute of Technology in Pasadena, Calif. “This approach is the most widely applicable way to generate large numbers of highly functional antitumor T cells.”

Different T cell functions are associated with distinct proteins. Heath and colleagues took a closer look at how genetically engineered T cells functioned or failed after being transferred into patients. To do this, they used a recently developed, multiplexed technology that gave them a high-resolution view of which function-associated proteins individual cells expressed.

The researchers analyzed T cells isolated from blood samples taken from three patients with melanoma at several time points after treatment with genetically engineered antimelanoma T cells. Each of the patients from whom samples were taken had exhibited a different level of response to the immunotherapy.

The most highly functioning genetically engineered antimelanoma T cells made up about 10 percent of the total population of transferred T cells.

“However, they dominated the immune response,” Heath said. “In other words, 10 percent of the cells are putting out 100 times more protein than the other cells.”

Although these highly functioning genetically engineered T cells had high tumor-killing capabilities when a patient first received them, those capabilities disappeared within two to three weeks.

“The genetically engineered T cells did recover their high functional capacity, but those functions no longer included tumor-killing,” Heath said. “However, there was another population of T cells that emerged at around one month that did exhibit tumor-killing characteristics.”

These new T cells appeared to be a byproduct, through a process known as epitope spreading, of the original genetically engineered, tumor-killing T cells the patient received, Heath explained. The researchers also discovered one potential cause for the transient response to T cell therapy. Results showed that as the patient’s own immune system recovered, after its initial depletion prior to therapy, those recovering T cells appeared to inhibit the antitumor immune response.

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Gene Profile May Help Identify Risk for Hormone-sensitive, Hormone-insensitive Breast Cancer

registration@aacr.org () — Tue, 19 Mar 2013 12:00:00 GMT

Levels of 13 genes elevated in unaffected breasts of women with hormone receptor-negative breast cancer.
Eight of the genes were associated with lipid metabolism.
Ability to identify those at risk may help tailor prevention strategies.

PHILADELPHIA — The overexpression or underexpression of a newly identified set of genes related to lipid metabolism may help physicians identify whether or not a woman is at risk for hormone receptor-positive or hormone receptor-negative breast cancer and to subsequently tailor prevention strategies appropriately, according to data published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

“Currently, three drugs can be used to prevent breast cancer in women who are at extremely high risk for the disease,” said Seema A. Khan, M.D., co-leader of the Breast Cancer Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago. “However, these drugs prevent only breast cancers that are sensitive to hormones, commonly referred to as estrogen receptor-positive breast cancers; they do not prevent breast cancers that are insensitive to hormones, or estrogen receptor-negative breast cancers.

“We should not expose women at risk for hormone-insensitive breast cancer to the side effects of preventive medications that we know will not work for them,” Khan said. “Moreover, if we knew who these women were, we could focus on them in terms of designing new studies to find a solution for preventing hormone-insensitive cancer.”

Khan and colleagues sought to find a way to identify women at risk for estrogen receptor-negative breast cancer by examining gene expression in the unaffected breasts of women who had a primary breast cancer of known estrogen-receptor status.

They used this approach because prior research has indicated that if women who have had cancer in one breast subsequently develop a cancer in their second breast, the second cancer is likely to have hormone-receptor status that resembles the first cancer.

Using this logic, Khan and colleagues performed fine-needle aspiration on the unaffected breasts of 15 women with estrogen receptor-positive breast cancer and 15 women with estrogen receptor-negative breast cancer. They validated their results in a second group of women: 12 with estrogen receptor-positive disease, 12 with estrogen receptor-negative disease and 12 healthy controls. The cases in each set were matched by age, race and menopausal status.

The researchers identified 13 genes with significantly higher expression levels in samples from estrogen receptor-negative women. Eight of these genes were associated with lipid metabolism.

“This was interesting because obesity is a breast cancer risk factor for postmenopausal women, but obese women are generally thought to be at increased risk for hormone-sensitive cancer,” Khan said. “We were surprised to see that some of these genes that are associated with lipid metabolism, or the metabolism of fats, are actually more highly expressed in the unaffected breasts of women with estrogen receptor-negative breast cancer.”

The researchers also found significant overexpression of four of the genes associated with lipid metabolism — DHRS2, HMGCS2, HPGD and ACSL3 — in estrogen receptor-negative samples when compared with healthy women. In estrogen receptor-positive samples, two different lipid metabolism-associated genes — UGT2B11 and APOD — were underexpressed.

“It will be a few more steps before this information is practically useful, but we are hoping that it can take us to a place where we can obtain a breast sample from healthy women, see that they are at risk for a certain type of breast cancer and tailor the prevention strategy accordingly,” Khan said.

# # #

Trio of Biomarkers May Help Identify Kidney Cancer in Early Stages

registration@aacr.org () — Mon, 11 Mar 2013 12:00:00 GMT

Biomarkers could help catch otherwise hard-to-detect cancer.
Three-marker assay has high sensitivity and specificity.
Researchers are seeking FDA approval.

PHILADELPHIA — A new immunoassay that tests for the presence of three biomarkers appears to be a valid screening method for the early detection of malignant kidney cancer, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Renal cell carcinoma, a malignant tumor arising from the kidney, is one of the most difficult forms of cancer to detect and treat properly because it remains silent until disseminating to other organs,” said Nam Hoon Cho, M.D., of the Department of Pathology at Yonsei University Health System in Seoul, Korea. “Furthermore, because imaging, which is high-cost, is seldom performed without any specific reasons, developing a blood-tumor biomarker is a great chance to detect the silent killer.”

The new immunoassay developed by Cho and colleagues from Genomine Inc. measured the levels of three potential biomarkers for kidney cancer: nicotinamide N-methyltransferase (NNMT), L-plastin (LCP1) and nonmetastatic cells 1 protein (NM23A).

Using this assay, the researchers measured concentrations of NNMT, LCP1 and NM23A in 189 plasma samples from 102 healthy controls and patients with benign tumors and 87 patients with kidney cancer. Plasma levels indicated that all three biomarkers were highly elevated in patients with kidney cancer. For example, the median level of NNMT concentration in healthy controls was 68 pg/mL compared with 420 pg/mL for patients with kidney cancer.

Next, the researchers tested the ability of the immunoassay to distinguish plasma samples from healthy controls and patients with kidney cancer using the same 189 plasma samples already tested. The results indicated that the three-marker assay was highly accurate. When it correctly identified 90 percent of the samples from healthy controls, it also correctly identified 94.4 percent of the samples from patients with kidney cancer.

To validate the accuracy of the test, the researchers blind tested an additional 100 plasma samples from 73 healthy controls and 27 patients with kidney cancer. In this analysis, 67 of the samples from the 73 healthy controls and all of the samples from patients with kidney cancer were classified correctly.

“If this biomarker is truly valid and accurate to detect renal cell carcinoma, a number of patients with renal cell carcinoma could potentially be saved through early diagnosis,” Cho said.

Cho and colleagues hope that this biomarker will soon be commercially available. They are currently working toward approval by the U.S. Food and Drug Administration.

# # #

AACR Announces Annual Meeting Press Conference Schedule

registration@aacr.org () — Thu, 07 Mar 2013 12:00:00 GMT

Press conferences will highlight key scientific breakthroughs.
Full press releases will be distributed, under embargo, on April 1.
Reporters who cannot attend in person can call in: 1 (800) 446-2782.

WASHINGTON, D.C. — The American Association for Cancer Research Annual Meeting 2013 will be held here April 6-10. To help reporters plan coverage of the meeting, the AACR Communications and Public Relations Department will host a series of press conferences throughout the week.

Final content, including embargoed press releases and other materials, will be distributed to registered reporters and other members of the media on April 1.

Press conferences will be held at the following times and locations:

Saturday, April 6, 2013:

1 p.m. ET, “Late Breaking Clinical Trials,” Room 153, Washington, D.C. Convention Center
3:30 p.m. ET, “Genomics and Predictors of Outcome,” Room 153, Washington, D.C. Convention Center

Sunday, April 7, 2013:

2 p.m. ET, “Treatment and Resistance to Targeted Therapies,” Room 153, Washington, D.C. Convention Center
5 p.m. ET, “Stand Up To Cancer,” Room 152, Washington, D.C. Convention Center

Tuesday, April 9, 2013:

9 a.m. ET, “AACR Policy Initiatives,” Room 153, Washington, D.C. Convention Center

During all press conferences, reporters who cannot attend in person can call in using 1 (800) 446-2782. For more information or to register for the meeting, please contact Jeremy Moore at jeremy.moore@aacr.org.

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Newly Identified Biomarkers May Help Predict Progression of Barrett's Esophagus to Esophageal Adenocarcinoma

registration@aacr.org () — Wed, 06 Mar 2013 12:00:00 GMT

Expression of most microRNAs was similar between the two conditions.
A small number were differentially expressed.
These microRNAs could be biomarkers for early diagnosis of progression.

PHILADELPHIA — A series of microRNA expression signatures that may help to define progression of the precancerous condition Barrett’s esophagus into esophageal adenocarcinoma was reported recently in Cancer Prevention Research, a journal of the American Association for Cancer Research.

“Once a rare cancer representing only 5 percent of all esophageal cancers in the United States, esophageal adenocarcinoma is the cancer with the fastest-rising incidence — six-fold increase in the past three decades — and currently comprises more than 80 percent of all new esophageal cancer cases in this country,” said Xifeng Wu, M.D., chair of the Department of Epidemiology, Division of Cancer Prevention and Population Sciences at The University of Texas MD Anderson Cancer Center, in Houston. “To reduce the mortality of esophageal adenocarcinoma, the best hope in the near term is to detect it at its early stage, or even better, to prevent the progression of esophageal adenocarcinoma from its premalignant lesion, which is called Barrett’s esophagus.”

Wu and colleagues evaluated microRNAs, which are a class of small ribonucleic acids in cells capable of regulating a large number of genes. Research has shown that aberrant expression of microRNAs is involved in cancer development.

The researchers compared hundreds of microRNAs in normal esophageal epithelia and in Barrett’s esophagus and esophageal adenocarcinoma tissues of different histological grades with distinct progression risks. They identified a number of differentially expressed microRNAs at each histological stage.

“The expression of microRNAs in Barrett’s esophagus and esophageal adenocarcinoma tissues was remarkably similar, indicating that the microRNA aberrations were very early events in the development of Barrett’s esophagus,” Wu said. “These aberrations in microRNA expression may drive other late events that ultimately lead to carcinoma formation.”

The researchers also identified a small number of microRNAs that were significantly different between Barrett’s esophagus and esophageal adenocarcinoma. Specifically, downregulation of the microRNA miR-375 and upregulation of five microRNAs of the miR-17-92 and homologue family seemed to differentiate Barrett’s esophagus and esophageal adenocarcinoma.

“Therefore, those patients with Barrett’s esophagus with low levels of miR-375 and/or high levels of the other five microRNAs we found to be upregulated in esophageal adenocarcinoma are at increased risk for malignant progression and should be under intensive surveillance, screening and treatment of their Barrett’s esophagus,” Wu said.

“Defining the protein-coding genes targeted by the differentially expressed microRNAs we identified may provide significant biological insights into the development of esophageal adenocarcinoma,” she added. “Moreover, these genes may themselves become promising biomarkers to predict Barrett’s esophagus progression as well as potential preventive and therapeutic targets.”

# # #

Visceral Fat Causally Linked to Intestinal Cancer

registration@aacr.org () — Wed, 06 Mar 2013 12:00:00 GMT

Loss of fat by surgical removal or a calorie-restricted diet reduced likelihood of developing intestinal tumors.
Differences were found between male and female mice.
Study emphasizes the need for strategies to reduce visceral fat.

PHILADELPHIA — Visceral fat, or fat stored deep in the abdominal cavity, is directly linked to an increased risk for colon cancer, according to data from a mouse study published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

“There has been some skepticism as to whether obesity per se is a bona fide cancer risk factor, rather than the habits that fuel it, including a poor diet and a sedentary lifestyle,” said Derek M. Huffman, Ph.D., postdoctoral fellow at the Institute for Aging Research at the Albert Einstein College of Medicine in Bronx, N.Y. “Although those other lifestyle choices play a role, this study unequivocally demonstrates that visceral adiposity is causally linked to intestinal cancer.”

Prior research has shown that obesity markedly increases the likelihood of being diagnosed with and dying from many cancers. Huffman and colleagues sought to determine if removing visceral fat in mice genetically prone to developing colon cancer might prevent or lessen the development of these tumors.

They randomly assigned the mice to one of three groups. Mice in the first group underwent a sham surgery and were allowed to eat an unrestricted “buffet style” diet, for the entirety of the study, which resulted in these mice becoming obese. Those in the second group were also provided an unrestricted diet and became obese, but they had their visceral fat surgically removed at the outset of the study. Mice in the third group also underwent a sham surgery, but were provided only 60 percent of the calories consumed by the other mice in order to reduce their visceral fat by dieting.

“Our sham-operated obese mice had the most visceral fat, developed the greatest number of intestinal tumors, and had the worst overall survival,” Huffman said. “However, mice that had less visceral fat, either by surgical removal or a calorie-restricted diet, had a reduction in the number of intestinal tumors. This was particularly remarkable in the case of our group where visceral fat was surgically removed, because these mice were still obese, they just had very little abdominal fat.”

The researchers then subdivided the groups by gender. In female mice, the removal of visceral fat was significantly related to a reduction in intestinal tumors, but calorie restriction was not. In male mice, calorie restriction had a significant effect on intestinal tumors, but removal of visceral fat did not.

“This suggests that there are important gender differences in how adiposity and nutrients interact with the tumor environment,” Huffman said. “In addition, the study emphasizes the need to promote strategies that reduce visceral fat in abdominally obese individuals.”

Huffman noted that more studies are needed to definitively uncover the mechanisms behind the causality between visceral fat and intestinal cancer, to determine how abdominal obesity and nutrient availability act independently during the stages of tumor promotion and progression, and to determine how other strategies to promote weight loss, such as bariatric surgery, affect cancer risk.

# # #

AACR Mourns Loss of Zora Brown: Prominent Cancer Research Advocate, Champion of Breast Cancer Awareness Among African-Americans

registration@aacr.org () — Mon, 04 Mar 2013 12:00:00 GMT

PHILADELPHIA — The American Association for Cancer Research (AACR) is deeply saddened by the loss of Zora Brown, a trustee for the AACR Foundation for the Prevention and Cure of Cancer, a breast and ovarian cancer survivor and a pioneering advocate for cancer research and breast cancer awareness among minorities. Ms. Brown, who passed away Sunday, March 3 at 63 years of age, was also the founder and chairperson of Cancer Awareness Program Services (CAPS) and the Breast Cancer Resource Committee (BCRC), an organization dedicated to lowering the breast cancer mortality rate among African-Americans.

“There is a hole in our hearts as we mourn the loss of Zora Brown, who despite her many years of dealing with two cancers and multiple relapses, maintained an amazing and courageous spirit that inspired everyone around her,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the American Association for Cancer Research. “Her life’s work as a cancer advocate has been extremely important in increasing public awareness about cancer, especially among women. Our lives have been enriched by knowing her. In her memory and honor, we will do our utmost to work even harder to expedite the prevention and cure of this disease that takes so many.”

At the end of her life, Ms. Brown was living with stage III ovarian cancer, but she was first diagnosed with breast cancer in 1981, at just 32, and then again in 1997. Her experience with cancer led her to devote her life as an advocate for women, and for African-American women in particular, with breast and ovarian cancers.

In 2011, Ms. Brown shared her story with the world in the AACR Cancer Progress Report 2011. In June 2012, she testified at a U.S. Senate Cancer Coalition forum where she explained that cancer, which will strike one out of two men and one out of three women in their lifetimes, was a journey that began before she was born because of a family history and genetic predisposition.

“The AACR and cancer research community lost an amazing and gracious woman with the passing of Zora Brown. I cannot stress enough the importance of her work as an advocate for cancer research. She, along with other advocates, are the unsung heroes in the fight against cancer,” said AACR President Frank McCormick, Ph.D., director of the UCSF Helen Diller Family Comprehensive Cancer Center. “Zora’s strength in battling her cancers and her passion for advocating for women with cancer were an inspiration to us all. She will be dearly missed but certainly never forgotten.”

Brown also served with distinction as a member of the board of trustees for the AACR Foundation for the Prevention and Cure of Cancer since 2008 where her voice and resolve as a cancer survivor and advocate were richly appreciated.

“We have just lost a great leader in the fight against cancer. In spite of her own challenges with cancer, she untiringly extended her hands to help others and was a fervent promoter of the prevention and cure of breast cancer,” said Yuet Wai Kan, M.D., D.Sc., AACR Foundation Board Chairman and professor of hematology, University of California, San Francisco. “She was also a strong advocate for cancer research through congressional testimony. Her eloquence and clarity of purpose will be missed by all trustees of the AACR Foundation.”

After her first breast cancer diagnosis led to a mastectomy, Ms. Brown learned that cancer mortality rates for African-American women were continuing to increase while rates were decreasing for Caucasian women. Alarmed by these statistics, she formed the BCRC in 1989, an advocacy organization that vowed to lower the mortality rate among African-Americans by the end of this century.

Ms. Brown graduated from Oklahoma State University in 1969 with a bachelor’s degree in business administration. Following this she obtained a job as secretary at the Pharmaceutical Manufacturers’ Association and then took a position with the Ford Motor Company, where she served for six years in the lobbying office.

In 1976, Ms. Brown took an administrative assistant’s post at the White House in a division concerned with women’s programs during the nationwide efforts to ratify the Equal Rights Amendment. During this time she formed a lifelong friendship with First Lady Betty Ford. She continued her government service as director of Minority Enterprise at the Federal Communications Commission.

After founding BCRC, Ms. Brown began her role as an activist speaking in African-American churches with events that initially included Marilyn Quayle.

In the late 1980s, she partnered with the Revlon Company Foundation; Lilly Tartikoff, wife of the then-NBC president; Phylicia Rashad; and Jane Pauley to produce “Once a Year…For a Lifetime,” a documentary movie explaining the benefits of regular mammography that made its television debut on Nov. 16, 1990.

In 1991, President Bush appointed her to the National Cancer Advisory Board (NCAB), which is an 18-member advisory body of outside experts whose primary task is to advise the secretary of Health and Human Services, the director of the National Cancer Institute (NCI), and ultimately the president of the United States on a range of issues affecting the nation’s cancer program and, specifically, NCI operations. She served on the board until 1998. Due in part to Ms. Brown’s influence, Congress appropriated $500,000 for breast and cervical screening for low-income, uninsured, inner-city women.

As part of the BCRC, Ms. Brown organized the CAPS in 1992, to institute comprehensive educational and prevention programs focusing on cancers affecting women. In 1993, she established “Rise-Sister-Rise,” an all-African-American, free gathering on Saturday mornings in local venues that taught women the rules of healthy living and cancer prevention.

Ms. Brown has been recognized widely for her work in breast cancer awareness among minorities. In 1990, she was honored by Senator Fred Hollings of South Carolina, who invited her to become a board member of the Hollings Cancer Center at the Medical University of South Carolina.

She has also appeared in a Washington Post feature called “Portraits of the City,” which lauded her for her work.

In 1992, she received the Marilyn Trist Robinson Community Service Award from the Washington Association of Black Journalists. In the same year she received the Susan G. Komen Community Service Award and the Breast Cancer Award from the National Women’s Health Resource Center. In 1993, she received the Gretchen Post Award and was cited by the U.S. Senate in 1995.

“She was so full of wonderful life every time we interacted. These tragically too-early losses inspire us to redouble our endeavors against cancer,” said AACR Past President Elizabeth H. Blackburn, Ph.D., Nobel laureate and the Morris Herzstein professor in biology and physiology in the Department of Biochemistry and Biophysics at the University of California, San Francisco.

# # #

Obesity, Physical Inactivity Linked With Risk for Certain Molecular Subtype of Colorectal Cancer

registration@aacr.org () — Tue, 26 Feb 2013 12:00:00 GMT

Obesity increased risk; physical activity lowered risk.
Data consistent with prior research linking exercise to decreased mortality.
Research on colon cancer should incorporate heterogeneity of disease.

PHILADELPHIA — An increasing body mass index was associated with a higher risk for colorectal cancer with a specific molecular characteristic, and inversely, physical activity was linked to a decreased risk for that same cancer, according to data published in Cancer Research, a journal of the American Association for Cancer Research.

“We know that exercise and avoiding obesity decrease colorectal cancer risk, but little is known about why,” said Shuji Ogino, M.D., Ph.D., associate professor of pathology at Dana-Farber Cancer Institute and associate professor in the Department of Epidemiology at Harvard School of Public Health in Boston, Mass. “In this study, we used a biomarker named CTNNB1, which is a molecule implicated in cancer and obesity, to divide patients into two groups, CTNNB1-positive and CTNNB1-negative.”

Ogino and colleagues used data from more than 100,000 women from the Nurses’ Health Study and more than 45,000 men in the Health Professionals Study to examine whether there was an association between body mass index (BMI) or exercise activity and colorectal cancer risk according to CTNNB1 expression status.

Among the study population, 2,263 individuals were diagnosed with colorectal cancer during follow-up. Tumor CTNNB1 expression data were available for 861 of these individuals, and 54 percent of these tumors were negative for CTNNB1 and 46 percent positive for the biomarker.

Increasing BMI by a 5.0 kg/m² increment was associated with a 34 percent higher risk for CTNNB1-negative cancer, but was not associated with CTNNB1-positive cancer. In contrast, increasing physical activity level was associated with a significantly lower risk for CTNNB1-negative cancer. It was not associated with CTNNB1-positive cancer.

“Our results provide additional evidence for a causal role of obesity and a physically inactive lifestyle in a specific molecular subtype of colorectal cancer,” Ogino said. “If physicians are able to identify individuals who are prone to develop CTNNB1-negative cancer, then it would be possible to strongly recommend physical activity.”

In addition, the data indicated that CTNNB1 could be a potential target for chemoprevention and treatment, according to Ogino. He called for more population-based, large-scale databases to facilitate molecular pathological epidemiology research.

“Currently, most population-based studies do not take tumor heterogeneity into consideration, and typically colon cancer is treated as a single disease,” Ogino said. “We need to integrate molecular pathology and epidemiology in education and research to facilitate integrative science and improve public health.”

# # #

AACR Congratulates Recipients of the Inaugural Breakthrough Prize in Life Sciences

registration@aacr.org () — Fri, 22 Feb 2013 12:00:00 GMT

AACR President-elect Charles L. Sawyers, M.D. is among the 11 winners.

PHILADELPHIA — The American Association for Cancer Research congratulates the recipients of the first Breakthrough Prize in Life Sciences. Nine of the 11 recipients are members of the AACR, including President-elect Charles L. Sawyers, M.D.

The award recognizes scientists for their achievements in the life sciences field and provides them with the opportunity and freedom to continue their important pioneering research into curing disease. Each recipient will receive $3 million.

“The AACR extends sincere congratulations to each winner of this award,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “All of these scientists have made remarkable contributions in their fields. Each one undoubtedly has more to offer the scientific community and the public, and this award will ensure that they continue to pursue their cutting-edge research. We are especially proud to see so many AACR members recognized, because their commitment to accelerating research to prevent and cure cancer is invaluable.”

The following AACR members received the Breakthrough Prize in Life Sciences:

David Botstein, Ph.D., Anthony B. Evnin Professor of Genomics, Princeton University, Princeton, N.J.
Lewis C. Cantley, Ph.D., director, Weill Cornell Medical College and New York-Presbyterian Hospital Cancer Center, New York, N.Y.; Stand Up To Cancer Dream Team Leader, Targeting the PI3K Pathway in Women’s Cancers
Hans Clevers, M.D., Ph.D., director, Hubrecht Institute, Utrecht, Netherlands
Napoleone Ferrara, M.D., Ph.D., Genentech Fellow, University of California, San Diego, Calif.
Titia de Lange, Ph.D., Leon Hess Professor, Rockefeller University, New York, N.Y.
Eric S. Lander, Ph.D., director, Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, Mass.
Charles L. Sawyers, M.D., chair, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, N.Y.; SU2C-PCF Prostate Cancer Dream Team Co-Leader, Precision Therapy for Advanced Prostate Cancer; AACR president-elect
Bert Vogelstein, M.D., professor of oncology and pathology, Johns Hopkins University, Baltimore, Md.
Robert A. Weinberg, Ph.D., professor of biology, Massachusetts Institute of Technology, Cambridge, Mass.

The AACR also applauds the additional two recipients, Cornelia I. Bargmann, Ph.D., Torsten N. Wiesel Professor in the Laboratory of Neural Circuits and Behavior, Rockefeller University, and Shinya Yamanaka, M.D., Ph.D., investigator, Gladstone Institutes, San Francisco, Calif. and Kyoto University, Japan, and 2012 Nobel Prize recipient.

The Breakthrough Prize in Life Sciences Foundation was established by Yuri Miller, an entrepreneur and philanthropist, Sergey Brin, a Google co-founder, Anne Wojcicki, the founder of the genetics company 23andMe, and Mark Zuckerberg, the founder of Facebook. In the future, the foundation plans to award five prizes annually. Although many of this year’s recipients have worked in cancer research, the prize is open to scientists working in all fields of medicine and biology.

# # #

Biomarker May Identify Neuroblastomas With Sensitivity to BET Bromodomain Inhibitors

registration@aacr.org () — Thu, 21 Feb 2013 12:00:00 GMT

MYCN gene is commonly amplified in neuroblastoma and associated with poor prognosis.
A BET bromodomain inhibitor downregulated MYCN expression.
The drug prolonged survival in three animal models of MYCN-amplified neuroblastoma.

PHILADELPHIA — Neuroblastoma, the most common malignant tumor of early childhood, is frequently associated with the presence of MYCN amplification, a genetic biomarker associated with poor prognosis. Researchers have determined that tumors containing MYCN amplification are sensitive to a new class of drugs, BET bromodomain inhibitors.

The researchers made this discovery in a preclinical study, which was funded in part by a Stand Up To Cancer Innovative Research Grant and was published in Cancer Discovery, a journal of the American Association for Cancer Research.

“BET bromodomain inhibitors are a class of drugs that many researchers are hopeful may offer a new therapeutic option for treating patients with certain cancers,” said Kimberly Stegmaier, M.D., assistant professor of pediatrics in the Department of Hematology/Oncology at Dana-Farber/Children’s Hospital Cancer Center in Boston, Mass. “The challenge has been identifying biomarkers that can help direct clinical translation of these drugs by pinpointing those patients with the highest likelihood of response.”

To identify genetic biomarkers of responsiveness to BET bromodomain inhibitors, Stegmaier and colleagues screened more than 600 cancer cell lines with known genetic characteristics for sensitivity to a prototypical BET bromodomain inhibitor.

Using this high-throughput, cell-based screening process, the researchers found that neuroblastoma cells in which the MYCN gene was amplified were sensitive to BET bromodomain inhibitors.

“Neuroblastoma is a devastating childhood cancer, and only a minority of children with high-risk disease will be cured with currently available treatments,” Stegmaier said. “Prior research has shown that MYCN amplification is common in neuroblastoma, but it has been an elusive drug target.”

To further validate their findings, the researchers tested a BET bromodomain inhibitor, from the laboratory of James E. Bradner, M.D., at the Dana-Farber Cancer Institute, using cultured MYCN-amplified neuroblastoma cell lines and three animal models of MYCN-amplified neuroblastoma. Together, they found that the drug decreased levels of MYCN protein in cultured cells, and that this led to impaired cell growth and cell death. In each animal model, including a mouse model of neuroblastoma that is known to be resistant to many standard therapies, the drug was shown to have anti-tumor effects and to prolong survival.

“My Stand Up To Cancer grant, which focused on modulating difficult drug targets in childhood cancers, was instrumental to us being able to do this exciting work,” Stegmaier said. “These types of studies are generally considered high-risk, particularly because they start with unbiased screening, and they are generally less likely to be supported by traditional sources of funding.”

# # #

New Drug Combination Could Prevent Head and Neck Cancer in High-risk Patients

registration@aacr.org () — Tue, 19 Feb 2013 12:00:00 GMT

Preclinical combination of an EGFR inhibitor and a COX-2 inhibitor was effective.
Advanced oral precancerous lesions were eliminated in three patients.
Drug combination could be a new strategy to prevent head and neck cancers.

PHILADELPHIA — A new drug combination shows promise in reducing the risk for patients with advanced oral precancerous lesions to develop squamous cell carcinoma of the head and neck. The results of the study, which included preclinical and clinical analyses, were published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

“Squamous cell carcinoma of the head and neck (SCCHN) is the most common type of head and neck cancer,” said Dong Moon Shin, M.D., professor of hematology, medical oncology and otolaryngology at Emory University School of Medicine, and director of the Cancer Chemoprevention Program at Winship Cancer Institute at Emory University in Atlanta, Ga. “The survival rate for patients with SCCHN is very poor. An effective prevention approach is desperately needed, especially since we can identify patients who are at extremely high risk: those with advanced oral precancerous lesions.”

Based on prior research suggesting a role for epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in promoting SCCHN, Shin and colleagues believed combining an EGFR inhibitor and a COX-2 inhibitor could provide an effective chemopreventive approach.

They found that the combination of the EGFR inhibitor erlotinib and the COX-2 inhibitor celecoxib was more effective for inhibiting the growth of human SCCHN cell lines compared with either drug alone. In addition, treating mice with the drug combination prior to transplanting them with human SCCHN cells more effectively suppressed cancer cell growth than did pretreating the mice with either drug alone.

Based on these preclinical analyses, Shin and colleagues initiated a phase I chemoprevention trial. Eleven patients with advanced oral precancerous lesions were assigned to treatment with erlotinib and celecoxib. Tissue samples from the patients were obtained and evaluated pathologically at three, six and 12 months after therapy initiation. Biopsies at baseline and follow-up were available for seven patients.

Pathologic examination of the biopsies indicated that three of the seven patients had a complete pathologic response; that is, there was no longer evidence of the precancerous lesions in the follow-up biopsy sample. Among the other patients, two had a partial pathologic response and two had progressive disease.

“Finding that this drug combination caused some advanced premalignant lesions to completely disappear was great news,” said Shin. “Advanced premalignant lesions rarely regress, so our data are proof-of-principle that a combination chemopreventive strategy with molecularly targeted agents is possible.”

Several patients dropped out of the trial because of severe adverse side effects, according to Shin. “Prevention is not achieved through short-term treatment,” he said. “So, we need to investigate the safety and toxicity of this combination further before planning a large-scale trial. We are also looking to combination therapies using less toxic or nontoxic agents, such as natural compounds.”

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

AACR Hosts Congressional Briefing on Cancer Progress, NIH Funding

registration@aacr.org () — Tue, 12 Feb 2013 12:00:00 GMT

Briefing contained updated data on economic impact of NIH funding.
Research leaders and patients addressed cancer progress.
High-resolution photos available to the media.

WASHINGTON, D.C. — The American Association for Cancer Research hosted a briefing on Feb. 12 for members of Congress and their legislative staffs that highlighted progress in cancer research and treatment as well as challenges created by decreased levels of funding.

The briefing was held in the Rayburn Building on Capitol Hill as the threat of sequestration looms. Unless Congress acts before March 1, funding for the National Institutes of Health (NIH) will decline by 5.1 percent, potentially resulting in a loss of more than 20,500 jobs and $3 billion in new economic activity, according to a report from United for Medical Research.

The American Association for Cancer Research (AACR), a member of United for Medical Research, highlighted the report as part of its briefing. The report estimates that NIH funding currently supports more than 402,000 jobs and $57.8 billion in economic output nationwide.

“It is imperative that funding for medical research through the NIH be regarded as a priority investment for our nation,” said Jon Retzlaff, M.P.A., M.B.A., managing director of the Office of Science Policy and Government Affairs at the AACR. “The frustrating reality is that our ability to deliver on the promise of science to patients is in great jeopardy due to both a decade of stagnant budgets and the looming threat of sequestration. We have reached a crisis point.”

The briefing was part of an ongoing effort by the AACR, United for Medical Research and approximately 100 other organizations to draw attention to the funding crisis and its impact through the Rally for Medical Research. These groups will host the Rally that is expected to draw more than 10,000 people to the steps of the Carnegie Library in Washington, D.C., on April 8, 2013, at 11 a.m.

It is estimated that each year more than 1.6 million Americans receive a cancer diagnosis and more than 580,000 will die of the disease. Due to advances in research and treatment, however, there are now nearly 14 million cancer survivors in the United States.

At Tuesday’s briefing, congressional staffers heard from Douglas Lowy, M.D., deputy director of the National Cancer Institute (NCI), a part of the NIH. Lowy highlighted statistics showing that cancer mortality rates have declined over the past 10 years for most cancers, but the decline has not been seen across all cancers and it has not been shared by all racial and ethnic groups or genders.

“Basic research supported by the NCI is the main engine of discovery that will lead to future breakthroughs in the fight against cancer,” said Lowy.

Unfortunately, while the budget for the NCI in fiscal year 2012 was approximately $5 billion, in any year most of that funding is already committed to ongoing projects and annual increases have not kept pace with inflation. According to Lowy, only around 15 percent of new grant applications receive funding.

“The key thing to remember about basic research is that only the public sector can really invest in it because the horizon line of the private sector is simply too short,” said Lowy.

Lowy cited the National Lung Screening Trial as an example of publicly funded research, which was conducted over approximately 10 years at a cost of more than $250 million. The trial, which was published in the New England Journal of Medicine in 2011, indicated that for current and former smokers, low-dose CT screening reduces lung cancer mortality by 20 percent.

Anna D. Barker, Ph.D., professor and director, Transformative Healthcare Networks, and co-director, Complex Adaptive Systems Research at Arizona State University, said one of the many examples of government-funded breakthroughs is The Cancer Genome Atlas.

“The data generated are helping researchers understand how these changes interact to drive different cancers, and they are laying the foundation for improving cancer prevention, early detection and treatment,” said Barker, a former deputy director of the NCI.

Barker was followed by Ken Anderson, M.D., director, Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute and Kraft Family professor of medicine at Harvard Medical School in Boston, Mass.

Anderson highlighted recent progress in blood cancers, which has made myeloma a “chronic disease for many patients,” Anderson said. According to Anderson, agents like bortezomib, the immunomodulatory drug lenalidomide, carfilzomib and pomalidomide have resulted in demonstrable patient benefit.

“Without NIH/NCI funding, this amazing progress simply would never have happened,” said Anderson. “Importantly, the lessons of myeloma apply to other blood cancers. Indeed, the mechanisms of disease are common, allowing for fast-forwarding progress in the development of new, more effective treatments.”

Anderson’s presentation was followed by M. Robert Carr, a former United States Congressman from Michigan, who was treated by Anderson for multiple myeloma in 2007. Carr was treated with bortezomib, a newly approved drug at the time. He has been cancer-free since 2008.

“Cancer does not discriminate. It can strike anyone—no age, gender, race, ethnicity or even political affiliation makes you immune to developing cancer,” said Carr. “As a result of the dedicated work of cancer and biomedical researchers like our panelists today, the progress has been remarkable.”

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New Fellowship Opportunity for Clinical/Translational Sarcoma Research

registration@aacr.org () — Mon, 11 Feb 2013 12:00:00 GMT

The AACR’s call for grant applications is open now through Feb. 26, 2013.

PHILADELPHIA — The American Association for Cancer Research (AACR) is pleased to announce a new partnership with the WWWW Foundation (QuadW) and the Communities Foundation of Texas. This partnership has established the QuadW Foundation-AACR Fellowship for Clinical/Translational Sarcoma Research grant opportunity, which will provide for a one-year grant to support innovative sarcoma research.

The grant recipient will receive $50,000 over the grant term, which begins July 1, 2013, and also complimentary registration to the AACR Annual Meeting 2013 to be held April 6-10 in Washington, D.C. Formal acceptance of the grant and announcement of the grant recipient will be observed at the Annual Meeting Grants Reception and Dinner on April 9.

“The AACR is very pleased to collaborate with the QuadW Foundation in offering this fellowship for sarcoma research,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “Although sarcomas are rare cancers, representing about 1 percent of all cancer cases diagnosed each year in the United States, there are 40 different subtypes of sarcoma and there is a compelling need for new therapeutic strategies to improve survival rates. This generous grant opportunity will have a profound effect on the career of a promising young investigator by providing funding for innovative, transformative research.”

The fellowship encourages and supports postdoctoral or clinical research fellows who are engaged in clinical or translational sarcoma research.

“QuadW seeks to facilitate progress in innovative sarcoma research. We are gratified that the AACR is interested in identifying and encouraging rising talent in this area, and we are delighted to add our support,” said Mac Tichenor, executive director of QuadW. QuadW – which stands for ‘What Would Willie Want?’ – was established in memory of Willie Tichenor, who died of osteosarcoma in 2006 at the age of 19. The foundation now honors Willie’s memory by working to find better treatments, and ultimately a cure, for sarcoma.

Candidates for the QuadW Foundation-AACR Fellowship for Clinical/Translational Sarcoma Research must possess a doctoral degree and cannot be enrolled in any program to obtain additional doctoral or professional degrees. At the start of the grant term, applicants must be within the first five years of a postdoctoral or clinical research fellowship and working under the auspices of a mentor at an academic, medical or research institution anywhere in the world. Grant applications will be reviewed by the AACR’s Scientific Review Committee, which is comprised of top scientists who are leaders in the field of sarcoma research. Applications must be received by noon ET on Feb. 26, 2013, using the proposalCENTRAL website. A paper application must also be submitted to: American Association for Cancer Research, 615 Chestnut Street, 17th Floor, Philadelphia, PA 19106, Attn: Hanna Hopfinger.

Learn more about the QuadW Foundation-AACR Fellowship for Clinical/Translational Sarcoma Research and application eligibility criteria.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information, visit www.AACR.org. Follow the AACR on Twitter @aacr #aacr and on Facebook http://www.facebook.com/aacr.org.

About the QuadW Foundation
The QuadW Foundation (What Would Willie Want?) was founded in memory of Willie Tichenor who died in 2006, at 19 years old, of osteosarcoma. Out of pain and loss, Willie’s family and friends established QuadW, redirecting the lens of hope that had focused on curing Willie to finding better treatments and cures for sarcoma, as well as supporting his passions of transformative mission and higher education. For more information, visit http://quadw.org/.

About the Communities Foundation of Texas
As the largest community foundation in Texas and one of the largest in the nation, Communities Foundation of Texas (CFT) works with families, companies and nonprofits to strengthen our community through a variety of charitable funds and strategic grant making initiatives. The foundation professionally manages nearly 900 charitable funds and has awarded over $1.2 billion in grants since its founding in 1953. For more information, visit http://www.cftexas.org/.

Media Contact:
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org

American Association for Cancer Research to Host Congressional Briefing About Progress in Cancer Research

registration@aacr.org () — Thu, 07 Feb 2013 12:00:00 GMT

Deputy Director of the National Cancer Institute, Dr. Douglas Lowy, will address the audience.
Event will showcase the AACR Cancer Progress Report, which is a call to action to make funding for the National Institutes of Health a national priority.
A foremost expert in blood cancers will describe progress in multiple myeloma.

WASHINGTON, D.C. — The American Association for Cancer Research will host a congressional briefing to highlight recent progress in cancer research and biomedical science, and call on Congress to avoid automatic cuts that would deal a devastating blow to the National Institutes of Health and National Cancer Institute.

The briefing will take place on Tuesday, Feb. 12, from 12-1:30 p.m. ET, in the Rayburn House Office Building, Room B-339. Reporters who wish to attend can register by contacting Jeremy Moore at jeremy.moore@aacr.org or (215) 446-7109.

AACR CEO Margaret Foti, Ph.D., M.D. (h.c.), will moderate the following distinguished panel of speakers:

Sen. Jerry Moran, R-Kan. (Invited)
Douglas R. Lowy, M.D., deputy director of the National Cancer Institute (NCI)
Anna D. Barker, Ph.D., professor and director of the Transformative Healthcare Networks and co-director of Complex Adaptive Systems Research at Arizona State University
Kenneth C. Anderson, M.D., director of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute and Kraft Family professor of medicine at Harvard Medical School
The Honorable M. Robert Carr, multiple myeloma survivor and former U.S. Representative from Michigan

During the briefing, panelists will present key advances in cancer research and cancer care as described in the AACR Cancer Progress Report 2012 and will highlight specific advances since the report in blood cancers like multiple myeloma.

Panelists will also discuss key initiatives at the NCI and the critical importance of funding to save more lives.

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MicroRNA Molecule May Serve as Biomarker, Target for Brain Metastases in Breast Cancer Patients

registration@aacr.org () — Tue, 05 Feb 2013 12:00:00 GMT

MicroRNA molecule called miR-7 decreased in highly metastatic cancer stem-like cells.
miR-7 attenuated cancer stem-like cells’ capacity for brain metastasis in mice.
MicroRNA molecule suppressed KLF4 expression.

PHILADELPHIA — Researchers have identified two molecules that could potentially serve as biomarkers in predicting brain metastases in patients with breast cancer, according to data published in Cancer Research, a publication of the American Association for Cancer Research.

Currently, most deaths from breast cancer are a result of metastatic disease. New research shows that cancer stem-like cells — commonly defined as cells within a tumor with the capacity to initiate a new tumor, proliferate rapidly, differentiate and cause chemotherapy resistance — may play a role in breast cancer metastasis.

“Recent research has shown that microRNAs are involved in tumor initiation and progression, and we hypothesized that they also may play a role in metastasis, particularly in relation to cancer stem-like cells,” said Kounosuke Watabe, Ph.D., associate director for basic science at the University of Mississippi Medical Center in Jackson, Miss.

Watabe and colleagues performed microRNA profile analysis on RNA extracted from cancer stem-like cells isolated from a human breast cancer cell line and two highly metastatic variants of this cell line.

“We found that miR-7 is a metastasis suppressor in cancer stem-like cells,” Watabe said. “When we increased expression of miR-7 in cancer stem-like cells from metastatic human breast cancer cell lines, it suppressed their metastatic properties.”

Next, the researchers examined the molecular pathway downstream of miR-7 to find its targets and discovered that miR-7 suppressed expression of KLF4.

“High expression of KLF4 was inversely associated with brain metastasis-free survival but was not associated with bone metastasis,” Watabe said. “This was confirmed in an animal model when we found that expression of miR-7 significantly suppressed the ability of cancer stem-like cells to metastasize to the brain but not the bone.”

Finally, the researchers tested tumor samples from patients with breast cancer whose disease metastasized to the brain. Results showed that miR-7 was downregulated and KLF4 was upregulated. The miR-7/KLF4 axis played a critical role in cancer stem-like cell brain metastasis, according to Watabe.

Few treatments currently exist for brain metastasis because few drugs can penetrate the blood–brain barrier, which prevents chemotherapy from reaching the brain.

“Cancer cells find the brain to be a kind of sanctuary where they can survive longer,” Watabe said. “It is possible that miR-7 and KLF4 may serve as diagnostic or prognostic markers, or therapeutic targets for the prediction of, or treatment of, brain metastasis.”

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Common Genetic Alteration Found in Head and Neck Cancers May Not be Key to Effective Treatment

registration@aacr.org () — Tue, 29 Jan 2013 12:00:00 GMT

Common pathway activation may not be “driving” tumor.
Deregulation of several genetic pathways may explain treatment resistance.

PHILADELPHIA — Although a large majority of head and neck cancers have a deregulation of the PI3K/AKT/mTOR pathway, data recently published in Cancer Research, a journal of the American Association for Cancer Research, indicated that deregulation of this pathway does not necessarily signify that the tumor is dependent on it for survival and progression.

Cancer, particularly of the head and neck, is highly heterogeneous, with a large number of genetic alterations rendering it resistant to specific targeted treatments. Because cancer is linked to genetic abnormalities, genomic and proteomic biomarkers are currently being used to design targeted therapeutic intervention for a variety of cancer indications.

Research has shown the PI3K/AKT/mTOR pathway is deregulated in a large majority of solid tumors. Treatment with mTOR inhibitors results in robust activity in certain cancer cell lines, but they are not effective in all patients. Researchers are currently using biomarkers to try to stratify patients for response to mTOR inhibitors.

“However, these technologies have limited success due to their inherent limitations in lack of clarity in distinguishing driver mutations in pathways from those of passengers,” said Pradip K. Majumder, Ph.D., of the division of cancer biology at Mitra Biotech, Bangalore, India.

Majumder and colleagues used a systems biology approach called tumor explant model to distinguish driver mutations, or those that are critical for a tumor’s survival, from passenger mutations. This distinction is important for stratifying patients for current treatments and for developing novel rational combinations of anticancer agents.

The researchers collected fresh tumor tissue from 22 patients with head and neck cancers and conducted ex-vivo explant experiments. They were able to identify responders to rapamycin, an mTOR inhibitor. However, a majority of the tumor samples did not have an antitumor effect after treatment with the mTOR inhibitor, possibly because rapamycin is known to activate the AKT pathway.

To combat the AKT pathway activation, Majumder and colleagues treated the tumor samples with rapamycin in combination with an AKT inhibitor. Rapamycin-induced AKT activation was reversed, but a subset of patients still failed to respond.

“While few tumors are dependent on only mTOR, others are dependent on both mTOR and AKT,” Majumder said. “However, a majority of the mTOR pathway-activated tumors seemed to not be dependent on this axis for survival or maintenance.”

Targeted phosphoproteomic characterization of tumors resistant to dual AKT/mTOR inhibitors showed that multiple pathways were supporting the tumors’ proliferation and survival and likely responsible for treatment resistance. This approach of combining ex vivo functional analyses with molecular profiling could potentially be used to stratify patients for appropriate combination therapy, according to Majumder.

“A majority of anticancer drugs fail in the phase II efficacy stage of clinical development due to a lack of technologies to identify and appropriately stratify patients according to their tumor pathway dependence,” Majumder said. “Using this approach, researchers may be able to develop a translational tool for further clinical development of novel anticancer drugs.”

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Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Treatment Targeting PI3K May Delay Resistance to Anti-HER2 Therapy in Breast Cancer Patients

registration@aacr.org () — Wed, 23 Jan 2013 12:00:00 GMT

Early use of PI3K inhibitors may prevent or delay treatment resistance.
Cancer cells resistant to anti-HER2 therapy had high levels of survivin.
Newly identified biomarker may help predict anti-HER2 therapy resistance.

PHILADELPHIA — Patients with HER2-positive breast cancer being treated with anti-HER2 therapy may be able to prevent or delay resistance to the therapy with the addition of a phosphatidylinositol-3 kinase inhibitor to their treatment regimens.

The data, published in Cancer Research, a journal of the American Association for Cancer Research, indicated that failure of the anti-HER2 antibody trastuzumab to block HER2 from activating the phosphatidylinositol-3 kinase (PI3K) signaling pathway can lead to resistance to treatment. Therefore, dual simultaneous inhibition of both HER2 and PI3K may prolong the use of anti-HER2 therapies in women with breast cancer.

“HER2 breast cancer is a subtype of breast cancer for which we have an increasing number of effective treatments, including trastuzumab, an antibody that targets HER2,” said Carlos L. Arteaga, M.D., director of the Breast Cancer Program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn. “Unfortunately, many breast cancer tumors learn how to resist this therapy.”

Arteaga and colleagues explored the possibility that aberrant signaling through the PI3K pathway was a mechanism of resistance to trastuzumab. They used breast cancer models of trastuzumab resistance with different modes of aberrant PI3K pathway activation, and treated the cells with a PI3K inhibitor with or without trastuzumab.

Inhibiting PI3K reduced cancer cells’ ability to proliferate and induced the death of trastuzumab-resistant cells. In addition, combining PI3K inhibitors with trastuzumab resulted in superior anti-tumor effects against trastuzumab-resistant, HER2-positive cells in xenografts compared with the PI3K inhibitor alone.

The investigators also conducted analyses to determine how the drug combination decreased resistance to trastuzumab.

“We found that the trastuzumab-resistant cells in which the PI3K pathway was activated had high levels of an anti-death protein called survivin,” Arteaga said. “This implied that if we could get levels of survivin to decrease, these cells would become sensitive to treatment.”

They also measured pretreatment levels of survivin in HER2-positive breast cancer tumors and found that higher pretreatment levels of the protein correlated with a poor response to therapy.

“This suggests that we could measure levels of survivin in tumors, and if they are high or do not decrease with treatment, we could predict that the tumor is resistant to anti-HER2 therapy and try to find alternative treatments,” Arteaga said.

Arteaga and colleagues plan to continue testing PI3K inhibitors, which are already in early clinical development, in combination with other HER2 drugs in breast cancer. They also plan to measure survivin levels in HER2-overexpressing breast cancer tumors to determine if levels can predict tumors that will benefit from combination treatment.

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New Test Predicted Presence of Harmful BRCA Mutations

registration@aacr.org () — Tue, 22 Jan 2013 12:00:00 GMT

Profile test demonstrated high sensitivity and specificity.
Test results could aid in clinical decision making.
May provide a quick, affordable alternative to current genetic testing.

PHILADELPHIA — A new multiple gene expression profile test was able to predict the presence of harmful BRCA1 or BRCA2 mutations in otherwise healthy women carrying the mutations, according to data published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

“This novel technology aims to provide a layer of information regarding the cell functionality aspect of BRCA mutations that could greatly enhance the doctor’s ability to identify high-risk carriers,” said Asher Y. Salmon, M.D., a breast cancer specialist at the Hadassah Hebrew University Medical Center in Jerusalem, Israel.

Women with a mutation in their BRCA1 or BRCA2 gene have a significantly increased risk for developing breast cancer or ovarian cancer, and for many of those at risk disease may develop at an early age. Researchers are investigating ways to detect these genetic mutations so women carrying the genes can consider taking measures to reduce their cancer risk or increase the chance for detecting cancer in its early stages.

“The current tool for mutation detection is gene sequencing, which is expensive, time-consuming and, in many cases, lacking clear and decisive clinical decision making information,” said Salmon. “In many cases, the current sequencing tool identifies a mutation, but we do not know if the mutation is neutral or harmful.”

According to Salmon, emerging evidence has revealed that cells with a mutation in one of the two copies of the BRCA1 or BRCA2 genes have a distinct gene expression profile when exposed to causes of DNA damage, such as radiation.

After collecting white blood cells from blood samples donated by nine healthy women with a mutated BRCA1 gene and eight healthy women with a mutated BRCA2 gene, Salmon and his colleagues cultured the cells and exposed them to radiation. They then extracted the total RNA from these cells and compared it to the total RNA from identically treated white blood cells from 10 healthy, noncarrier women.

About 1,500 genes were differentially expressed between carriers and noncarriers. They narrowed this list to 18 genes that were the most significantly differentiated between the two groups of women. The final narrowing was done with a validation study of a model using 21 of the newly identified genes and five control genes to predict the risk for carrying a mutation. They used blood samples from an independent group of 40 women who were carriers of mutated BRCA1 and/or BRCA2 and 17 noncarrier women. The model had a sensitivity of 95 percent and a specificity of 88 percent.

According to Salmon, this test can portray whether a patient carries a harmful mutation regardless of the patient’s ethnic origin or specific mutation. In addition, it is affordable and quick, he said.

“In wealthy societies, it can become a screening tool for identifying individuals with a very high susceptibility for carrying a mutation, and full sequencing can be reserved only for them,” Salmon said. “In societies in which sequencing is not feasible, this test can substitute for it with a very high accuracy rate.”

Salmon and colleagues are assembling a large validation study in Europe and North America to analyze the efficacy of the test in heterogeneous populations.

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AACR and CRI Announce Lloyd J. Old Award in Cancer Immunology

registration@aacr.org () — Tue, 22 Jan 2013 12:00:00 GMT

Award established to honor the Founding Father of Modern Tumor Immunology.

PHILADELPHIA and NEW YORK — The American Association for Cancer Research (AACR) and the Cancer Research Institute (CRI) have collaborated to establish a new award to honor the memory of the late Lloyd J. Old, M.D., a scientist whose lifetime of outstanding and innovative research in cancer immunology, as well as his decades of leadership in fostering the field, has had a far-reaching impact on cancer.

The recipient of the AACR-CRI Lloyd J. Old Award in Cancer Immunology will receive an honorarium of $10,000. In addition, he or she will be provided support to attend the AACR Annual Meeting 2013, to be held April 6-10 in Washington, D.C., and will be invited to give a 50-minute lecture during the meeting.

“The AACR is honored to collaborate with the Cancer Research Institute and offer this award in honor of Dr. Old, who was elected an honorary member of the AACR in 1995 and was CRI’s founding scientific and medical director,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “Dr. Old was a long-standing supporter of the AACR and an exceptional cancer immunologist who had a global impact on the field. He was internationally recognized as one of the founders and standard-bearers of the field of tumor immunology, and therefore became rightfully recognized as the ‘Father of Modern Tumor Immunology.’ Dr. Old’s vision and leadership brought basic and clinical investigators together, across both institutional and international borders, to take tumor immunology from animal models into clinical research and develop promising new cancer therapies.

“Cancer immunology is an exciting and growing field of research, and the AACR values its importance. This is evident not only in our joint partnership with CRI of this new award, but also in our recent announcement of the AACR’s newest journal, Cancer Immunology Research, which will launch online at the AACR Annual Meeting this spring,” added Foti.

Researchers in the field of cancer immunology explore the complex relationship between cancer and the immune system, with the goal of discovering immune-based solutions to curing cancer.

“Dr. Old’s prescient vision for the future of cancer treatment was rooted in his unwavering belief that the study of the immune system would ultimately yield the key to providing cancer patients with new and lifesaving treatment options,” said Jill O’Donnell-Tormey, Ph.D., chief executive officer and director of scientific affairs at CRI. “Many of Dr. Old’s own important discoveries laid the foundation for today’s successes in clinical cancer immunotherapy, and it is fitting that the AACR and CRI have so named an award that celebrates others who are unlocking the cancer-fighting secrets of our own immune system.”

Old’s research spanned 45 years — from proving that tumor immunity is dependent on specific tumor cell characteristics, first in animals and then in man, to detecting the first true human tumor antigens. He also developed cutting-edge techniques for monitoring human immunological responses to cancer vaccines, enabling the development of tumor-specific vaccines and targeted antibodies. Such innovations represent the most promising strategies for cancer therapies today.

When he began his career in 1958, tumor immunology was considered to be phenomenology based on single observations. However, through careful building of the field, principally by Old and his students, tumor immunology is now being understood at the molecular level. This fundamental knowledge is utilized to create novel immunotherapies that represent some of the greatest advances in cancer therapy since the development of the first chemotherapies.

Old’s contribution to science has extended far beyond his own research interests. Aside from his tireless dedication to developing the field of tumor immunology, Old was also a devoted and selfless mentor to hundreds of young researchers around the world for more than four decades.

The AACR-CRI Lloyd J. Old Award in Cancer Immunology was established to honor the testament of Old’s legacy. The award is intended to recognize an active cancer immunologist who, like Old, has done outstanding and innovative research in cancer immunology that has had a far-reaching impact on the field. The award is open to all cancer immunologists who are affiliated with any institution involved in cancer research, cancer medicine or cancer-related biomedical science anywhere in the world. Such institutions include those in academia, industry or government.

Candidates will be considered by a joint AACR-CRI Award Selection Committee on the basis of the significance of their innovative research, the impact of these discoveries on the cancer field and the degree with which their research has or will stimulate new directions in cancer immunology. All areas of cancer immunology will be considered for this award.

Learn more about the AACR-CRI Lloyd J. Old Award in Cancer Immunology. More about Old’s many distinguished accomplishments can be found online.

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Media Contacts:

AACR
Tara Yates
(215) 446-7110
Tara.Yates@aacr.org

CRI
Brian M. Brewer
(212) 688-7515, ext. 242
bbrewer@cancerresearch.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information, visit www.AACR.org. Follow the AACR on Twitter: @aacr #aacr. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.

About the Cancer Research Institute
The Cancer Research Institute (CRI), a nonprofit established in 1953, is the global leader in cancer immunology. Since its inception, CRI has invested hundreds of millions of dollars to support research conducted by more than 3,000 scientists and clinicians worldwide to understand the immune system and how it can be harnessed to conquer all cancers. This work has laid the foundation for nearly every major cancer immunotherapy breakthrough over the past half century. Guided by an international panel of the world’s leading immunologists and cancer immunologists, including three Nobel laureates and 29 members of the U.S. National Academy of Sciences, CRI provides essential funding to support every stage of discovery, from laboratory investigation to clinical trials of the most promising cancer immunotherapies for patients. CRI also sponsors a seminal international symposium on cancer immunology each year, hosts annual scientific colloquia dedicated to overcoming challenges in immunotherapy research and development, forges collaborative partnerships between academia and industry to facilitate the development pathway for novel immunotherapeutics, and presents special recognition awards to individuals who have made outstanding contributions to cancer research, patient care and public awareness. Through its sustaining support and leadership in the field, CRI is accelerating the development of safe and effective immunotherapies that stand to revolutionize the treatment of all cancers. For more information, visit http://cancerresearch.org or follow CRI on Twitter @CancerResearch.

New Model May Help Predict Response to Chemotherapy for Colorectal Cancer

registration@aacr.org () — Thu, 17 Jan 2013 12:00:00 GMT

Mathematical model measures stress level needed to produce cell death.
Model could eventually be applied in other cancers.

PHILADELPHIA — Scientists may be able to better predict which patients with colorectal cancer will respond to chemotherapy using a new mathematical model that measures the amount of stress required for a cancer cell to die without harming healthy tissue. The results of this study are published in Cancer Research, a journal of the American Association for Cancer Research.

“Our study demonstrates that systems medicine approaches (i.e., quantitative analysis of multiple factors in patients’ samples combined with mathematical modeling) have a significant advantage over other approaches in predicting therapy responses in patients,” said Jochen J.M. Prehn, Ph.D., director of the Centre for Systems Medicine at the Royal College of Surgeons in Ireland.

Apoptosis, or programmed cell death, is believed to be a hallmark of cancer resistance to chemotherapy. Prior research has shown that the key step in apoptosis, the process that leads to mitochondrial outer membrane permeabilization (MOMP) is controlled by different members of the BCL-2 family of proteins. Some family members promote apoptosis and some prevent it. In addition, those proteins that have the same effects on apoptosis work in parallel and can substitute for each other, which makes it difficult to predict whether cells are likely or unlikely to die.

To better inform decision-making in chemotherapy for colorectal cancer, Prehn and colleagues developed a tool that would incorporate patient-specific, molecular data sets. They studied the BCL-2 proteins, determined levels of the individual proteins and put the levels into a mathematical model that calculated what genotoxic stress level is needed to achieve apoptosis.

“Resistance of colon cancer cells in culture, as well as treatment responses of patients with stages 2 and 3 colon cancer, were critically determined by the calculated stress level required to undergo apoptosis,” Prehn said. “We found that individual patients had a high degree of heterogeneity in BCL-2 family protein levels and that this was a potential cause of the success or failure of adjuvant chemotherapy.”

Prehn and colleagues tested a clinical decision-making tool that they call DR_MOMP to determine its use in predicting treatment responses in patients with colon cancer. Using DR_MOMP, they were able to robustly predict patient outcome.

“This finding may provide a clinical decision-making tool that enables predictions of treatment responses in patients with colon cancer,” Prehn said. “As we provide a quantitative, dynamic analysis of the process of apoptosis, we can also calculate, for individual patients, the therapeutic window.”

The model could help predict how much genotoxic stress is required for a cancer cell to die before normal tissue is affected. Prehn and colleagues hope to validate DR_MOMP in other cancers and in larger patient cohorts.

“We need to develop easy and accessible protein profiling and modeling platforms that enable the implementation of this new technology in clinical trials and in pathology laboratories,” Prehn said.

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

AACR Calls for Applications for a New Stand Up To Cancer-Dutch Cancer Society Dream Team Grant

registration@aacr.org () — Wed, 16 Jan 2013 12:00:00 GMT

Up to €6 million grant available; application deadline is April 10, 2013

PHILADELPHIA – The American Association for Cancer Research (AACR) is now accepting applications for a Sta Op Tegen Kanker (“Stand Up To Cancer” in Dutch) Dream Team Translational Cancer Research Grant. This grant opportunity will offer up to €6 million (U.S. $8 million, at the current conversion rate) in research funding and is provided by Stand Up To Cancer (SU2C) and KWF Kankerbestrijding (the Dutch Cancer Society).

The grant provides four years of funding for a translational cancer research project that will address critical problems in patient care and deliver near-term patient benefit through investigation by a multidisciplinary, multi-institutional team of expert investigators. Research projects must be designed to accelerate the application of new preventive, diagnostic or therapeutic agents to the clinic, and may focus on particular organ sites or on specialized research areas.

Proposals for the Sta Op Tegen Kanker Dream Team Translational Cancer Research Grant must describe plans indicating how the work will be translated into the clinic. To maximize creativity, innovation and collaboration, the projects should span multiple disciplines and use modern biological tools to attack research questions in a coordinated way.

The leader of each project must be from a research institute located in the Netherlands. Co-leaders can be from research institutes in any country. Each project must include at least two research institutes located in the Netherlands and at least one research institute outside the Netherlands. At least 50 percent of the grant funds must be allocated to research conducted in the Netherlands.

Since the launch of SU2C in 2008, the AACR has played an integral role as SU2C’s scientific partner by providing scientific leadership, expert peer review and grants administration. To that end, the AACR will work closely with the Dutch Cancer Society on this project. A SU2C-KWF Joint Scientific Advisory Committee will conduct a unique, rapid and rigorous evaluation of the applications via a multistep scientific review process, and make recommendations on the final grant recipients. The committee is chaired by Arnold J. Levine, Ph.D., chairperson, along with Emile E. Voest, M.D., Ph.D., vice-chairperson, in addition to two distinguished scientists.

Proposals for Sta Op Tegen Kanker Dream Team Translational Cancer Research projects are due by April 10 via proposalCENTRAL.
For general information on eligibility criteria, the application process and other details about this Dream Team grant, visit www.aacr.org/su2cfunding. Inquiries may be directed to the Scientific Review & Grants Administration Department at (267) 765-1049 or su2c@aacr.org.

The Sta Op Tegen Kanker Dream Team Translational Cancer Research Grant is scheduled to be announced in the fall of 2013.

This grant is supported with money raised in connection with a 2010 and a 2011 Dutch version of the SU2C televised fundraising event, broadcast in the Netherlands in cooperation with the Dutch Cancer Society.

# # #

Media Contacts:

SU2C
Adam Pockriss
(212) 843-8286
apockriss@rubenstein.com

KWF (Dutch Cancer Society)
Stan Termeer
+ 31 (0) 205700538
STermeer@kwfkankerbestrijding.nl

AACR
Tara Yates
(215) 446-7110
Tara.Yates@aacr.org

About Stand Up To Cancer
Stand Up To Cancer – an initiative of the Entertainment Industry Foundation, a non-profit organization – began in the USA in 2008 with a landmark telecast on the ABC, CBS and NBC networks. The third U.S.-based telecast was broadcast on ABC, CBS, NBC, FOX and 22 cable networks on Sept. 7, 2012. Internationally, in addition to the Netherlands, Stand Up To Cancer launched in the United Kingdom with a four-hour live televised fundraiser on Channel 4 in collaboration with Cancer Research U.K. on Oct. 17, 2012.

Stand Up To Cancer raises funds to hasten the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. SU2C marshals the resources of the media and entertainment industries in the fight against this disease. Current members of the SU2C Council of Founders and Advisors (CFA) include Talk Show Host, Journalist and well-known Cancer Advocate Katie Couric; Sherry Lansing, Chairperson of the Entertainment Industry Foundation’s Board of Directors and Founder of the Sherry Lansing Foundation; EIF President and CEO Lisa Paulsen; EIF Senior Vice President Kathleen Lobb; Rusty Robertson and Sue Schwartz of the Robertson Schwartz Agency; Pamela Oas Williams, President of Laura Ziskin Productions and Executive Producer of Stand Up To Cancer’s In-house Production Team, and Nonprofit Executive Ellen Ziffren. All current members of the CFA were co-producers of the 2012 televised special. The late co-founder Laura Ziskin executive produced both the Sept. 5, 2008, and Sept. 10, 2010, broadcasts. SU2C was formally launched on May 27, 2008. Sung Poblete, Ph.D., R.N., has served as SU2C’s president and CEO since 2011.

SU2C’s “Dream Team” approach to funding translational cancer research enables scientists from different disciplines at research centers across the country and internationally to collaborate on projects geared toward getting new, less toxic treatments to patients as quickly as possible. Monies also support innovative cancer research projects that are often deemed “too risky” by conventional funding sources. Eighty-seven institutions are currently involved. As SU2C’s scientific collaborator, the American Association for Cancer Research, led by a prestigious SU2C Scientific Advisory Committee, provides scientific oversight, expert review of the research projects and grants administration. For more information, visit standup2cancer.org.

About the Dutch Cancer Society
The Dutch Cancer Society (DCS) is a nation-wide organization for cancer-related work in the Netherlands. We spend 80 percent of our budget to fund cancer research; 20 percent is spent on raising public awareness, providing information, as well as on prevention and patient support programmes. The DCS headquarter is located in Amsterdam; our professional staff amount to 140 persons. Over 100,000 volunteers support the DCS, whether through local or nation-wide fundraising, or scientific or policy advice in several councils and committees. We rely on nearly 1,600 local committees that organize our annual door-to-door knocking campaign to raise funds for the fight against cancer (annual revenue around €8 million). The DCS is supported by 880,000 donors and has been leading the fight against cancer ever since it was founded in 1949. Our goal is less cancer, more cure, and a better quality of life for cancer patients.

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional association dedicated to advancing cancer research and preventing and curing cancer. AACR membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org. Follow the AACR on Twitter: @aacr #aacr. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.

AACR and Kure It Announce Two Kidney Cancer Research Grant Recipients

registration@aacr.org () — Fri, 21 Dec 2012 12:00:00 GMT

Drs. William Y. Kim, of UNC, and James W. Mier, of Harvard, will each receive $250,000 grants to support innovative, translational kidney cancer research.

PHILADELPHIA — The American Association for Cancer Research and Kure It are pleased to announce that William Y. Kim, M.D., and James W. Mier, M.D., will each receive a 2012 AACR-Kure It Grant for Kidney Cancer Research.

Kim, assistant professor in the departments of medicine and genetics at the University of North Carolina School of Medicine, in Chapel Hill, and Mier, associate professor at Harvard Medical School in the division of hematology and oncology at Beth Israel Deaconess Medical Center, in Boston, Mass., will each receive $250,000 during the two-year grant term. In addition, Kim and Mier will receive complementary registration to the AACR Annual Meeting 2013, to be held April 6-10 in Washington, D.C., and will be recognized at the Annual Grants Reception and Dinner on Tuesday, April 9.

These grants are designed to provide support for innovative translational kidney cancer research designed to improve the survival and quality of life of patients with kidney cancer and, in turn, lead to individualized therapeutic options for the treatment or development of promising new kidney cancer therapies.

Kim’s project, “Defining the RCC [Renal Cell Carcinoma] Kinome for Target Discovery and Individualized Therapy,” aims to personalize kinase therapy based on the patient’s kidney tumor.

“Despite the fact that kidney cancer has very few activating mutations in kinases, they can be activated through alternate means and remain tenable therapeutic targets in renal cell carcinoma. We will use a novel, quantitative mass spectroscopy-based assay developed at University of North Carolina to assess the global activation state of the kinome and identify both novel as well as currently actionable targets,” said Kim, a faculty member of UNC Lineberger Comprehensive Cancer Center.

Mier’s research will explore the mechanism by which HDM2 antagonists and vascular endothelial growth factor-targeted drugs act together to block tumor angiogenesis and induce disease regression in renal cell carcinomas in his project, “HDM2/HDMX as a Therapeutic Target in Renal Cell Carcinoma.” His work will support the ongoing translational kidney cancer research at Dana-Farber/Harvard Cancer Center.

“I am honored to have been selected for this grant and am grateful to Kure It and the AACR for making the funds available. Everyone in my lab feels encouraged by this award. We are planning to use the funds to carry out preclinical studies of novel agents that may prove useful in patients with RCC. The AACR-Kure It funds will allow us to carry out studies that we might otherwise not have been able to undertake,” said Mier.

The expert scientific review committee, assembled by the AACR, received 44 high-caliber applications from independent investigators who proposed to develop and study new ideas and approaches that will have a direct application and relevance to patients with kidney cancer.

The AACR and Kure It are committed to collaboratively sustain the grant to award funding to the most promising kidney cancer research project.

# # #

Media Contacts:

AACR
Lauren Riley
(215) 446-7155
Lauren.Riley@aacr.org

Kure It
Karen Jones
(949) 428-7081
KarenJ@KureIt.org

Preventing Prostate Cancer Through Androgen Deprivation May Have Harmful Effects

registration@aacr.org () — Thu, 20 Dec 2012 12:00:00 GMT

Mice deficient in PTEN in the prostate developed stable precancers.
Androgen deprivation promoted progression to invasive prostate cancer.
Patients with PTEN-deficient prostate precancers may not benefit from androgen deprivation chemoprevention therapy.

PHILADELPHIA — The use of androgen deprivation therapies to prevent precancerous prostate abnormalities developing into aggressive prostate cancer may have adverse effects in men with precancers with specific genetic alterations, according to data from a preclinical study recently published in Cancer Discovery, a journal of the American Association for Cancer Research.

“The growth and survival of prostate cancer cells are very dependent on signals that the cancer cells receive from a group of hormones, called androgens, which includes testosterone,” said Thomas R. Roberts, Ph.D., co-chair of the Department of Cancer Biology at the Dana-Farber Cancer Institute and professor of biological chemistry and molecular pharmacology at Harvard Medical School in Boston, Mass.

Previous findings from two major randomized, placebo-controlled prostate cancer chemoprevention trials revealed that androgen deprivation therapy reduced the overall risk for low-grade prostate cancer. However, both trials also revealed a high cumulative risk for high-grade prostate cancers that has caused concern among experts.

High-grade prostatic intraepithelial neoplasia is a prostate abnormality that is considered to be a major precursor to prostate cancer. Loss of the tumor suppressor PTEN is detected in 9 to 45 percent of clinical cases.

Using a mouse model of PTEN-driven high-grade prostatic intraepithelial neoplasia, Roberts and his colleagues investigated whether surgical or chemical androgen deprivation could prevent the cancer precursor from progressing to more aggressive disease.

“When we castrated the animals, we thought the tumors would shrink and they did initially,” Roberts said. “However, they then grew back and became invasive.”

The results of this preclinical study suggest that prophylactic reduction of the most active form of androgen, or blocking androgen receptor function, might have unintended consequences in some men.

“Stretching our data even further, these findings suggest that as men age and their testosterone levels decrease, loss of testosterone might actually encourage indolent prostate tumors to become more aggressive,” Roberts said. “This suggests that testosterone supplements might be a good thing for the prostate, even though current wisdom suggests the opposite.”

Roberts noted that these results should be interpreted with caution because the prostate glands of mice are different from their human counterparts. More data on human tumors are needed to evaluate whether the data from this mouse study are applicable to men.

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

AACR Appoints Rick Buck as Senior Director of Communications and Public Relations

registration@aacr.org () — Wed, 19 Dec 2012 12:00:00 GMT

PHILADELPHIA — The American Association for Cancer Research has appointed Rick Buck as senior director of communications and public relations. Buck, who has more than 20 years of experience in health care communications, will oversee the communications and public relations department, as well as Cancer Today, the AACR’s consumer magazine that provides information and inspiration to cancer patients, survivors, and their family and friends.

“I am thrilled to welcome Rick to the AACR. He comes to us with a world of knowledge in health care communications and public relations. His experience, expertise and enthusiasm for our mission will be very valuable to the AACR,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “I am confident that Rick will help increase public awareness of the important scientific advances taking place in the field of cancer research, and also highlight the need for increased funding for cancer research and biomedical science.”

Prior to joining the AACR, Buck was chief communications officer and director of communications at BAYADA Home Health Care in Moorestown, N.J. Earlier in his career, he served as vice president of corporate communications for the AmeriHealth Mercy Family of Companies in Philadelphia, Pa., vice president of marketing communication at Home Medical of America in Cherry Hill, N.J., director of marketing communications at AmeriPath in Riviera Beach, Fla., and public relations manager for NovaCare in King of Prussia, Pa.

“I am honored and excited to join the AACR and help lead its communications and public relations strategic initiatives,” said Buck. “The AACR and its members are making extraordinary advances and measurable progress in cancer research. One of our goals will be to significantly raise public and policymaker awareness of this critical work, its impact and the need to strengthen funding for cancer research. I look forward to telling the AACR story, continuing to raise its profile in the public arena, and leading our efforts to consistently and clearly communicate the AACR’s mission to prevent and cure cancer through research, education, communication and collaboration.”

Buck is also former board chair and current member of the Public Relations Society of America (PRSA) Health Academy, director-at-large of the Philadelphia PRSA and business advisory board member of the Rowan University Rohrer College of Business in Glassboro, N.J. He received his bachelor’s degree in communications from Rowan University.

# # #

AACR's Cancer Today Magazine Received the 2012 Silver Ozzie Award

registration@aacr.org () — Tue, 18 Dec 2012 12:00:00 GMT

PHILADELPHIA — Cancer Today, a publication of the American Association for Cancer Research that provides information and inspiration to cancer patients, survivors, and their family and friends, was honored with a prestigious FOLIO: magazine silver Ozzie Award.

“We are delighted that Cancer Today received such an honor with this silver award,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “The new content and redesign of the magazine have provided patients and their families with the resources they need to stay informed about the latest developments in cancer research, treatment and care.”

The magazine’s December 2011 issue was awarded the silver Ozzie Award for the Best Redesign under the association/nonprofit category at the annual Eddies and Ozzies gala, held recently at the Marriott Marquis in New York, N.Y. The award recognizes an outstanding redesign of an existing publication.

Cancer Today is an authoritative resource for cancer patients, survivors, and their family members and friends as they face the challenges of diagnosis, treatment, survivorship and caregiving. Nearly 12 million Americans are cancer survivors, and Cancer Today provides this community with stories about patients who are dealing with cancer, information about developments in cancer therapy and research, and useful advice to help readers navigate the medical, practical and emotional issues surrounding cancer.

“I’m excited and honored that Cancer Today has been recognized with this prestigious Ozzie award,” said Jessica Gorman, executive editor of Cancer Today. “The redesign of the magazine is helping us reach more patients, survivors and their families than ever before with in-depth and reliable reporting that helps readers become active players in their cancer care or the care of their loved ones.”

FOLIO: Eddie and Ozzie Awards represent the largest awards competition in magazine publishing, and the only competition for all magazines and their websites. The Ozzies recognize excellence in magazine design, and the Eddies recognize editorial excellence. More than 2,000 entries from business-to-business, consumer, association/nonprofit, custom and supplemental annual or one-shot publications were received.

In redesigning the magazine, the Cancer Today editorial team worked with Bates Creative Group in Silver Spring, Md.

# # #

Hard-to-treat Myc-driven Cancers May Be Susceptible to Drug Already Used in Clinic

registration@aacr.org () — Fri, 14 Dec 2012 12:00:00 GMT

The mTORC1 inhibitor everolimus is used to treat various medical conditions.
Everolimus prevented disease development in a mouse model of Myc-driven lymphoma.
Treatment led to tumor regression in mice by inducing cellular senescence.

PHILADELPHIA — Drugs that are used in the clinic to treat some forms of breast and kidney cancer and that work by inhibiting the signaling molecule mTORC1 might have utility in treating some of the more than 15 percent of human cancers driven by alterations in the Myc gene, according to data from a preclinical study published in Cancer Discovery, a journal of the American Association for Cancer Research.

“More than 1 million people diagnosed with cancer each year have a tumor driven by alterations in the Myc gene,” said Grant A. McArthur, M.D., Ph.D., professor of translational research at the Peter MacCallum Cancer Centre in Melbourne, Australia. “However, it has proven impossible to develop drugs that effectively target Myc.

“One of Myc’s functions is to regulate cell growth. Because mTORC1 is also a regulator of cell growth, we hypothesized that inhibiting mTORC1 with the drug everolimus might suppress Myc-driven tumor initiation and growth.”

McArthur and his colleagues tested their hypothesis in a mouse model of Myc-driven lymphoma and found that treatment with everolimus provided strong protection against disease: only four of 33 mice treated with everolimus developed lymphoma, while 22 of 34 mice treated with placebo developed the disease.

In addition, treatment with everolimus led to tumor regression and significantly improved survival compared with placebo in mice with established lymphomas. However, all of these mice eventually relapsed as a result of the growth of lymphoma cells resistant to the effects of everolimus.

“These data confirmed our hypothesis that mTORC1 inhibition could suppress Myc-driven tumor initiation and growth,” said McArthur. “The surprise was found in how mTORC1 inhibition led to tumor regression. We had expected that it would trigger cancer cells to die by a cellular process known as apoptosis, but we found that this was not the case.”

Detailed analysis of the tumors indicated that everolimus caused tumor regression by inducing cellular senescence.

According to McArthur, normal cells protect themselves when cancer-driving genes are switched on by entering a state called senescence. When cancers develop, they have found ways to overcome this safeguard. “Our data indicate that one way in which cancers bypass senescence, in particular senescence induced by Myc, is through a signaling pathway involving mTORC1,” he said.

Resistance to everolimus treatment in mice with established lymphomas was associated with loss of the function of p53, a protein known to help suppress tumor formation and growth.

“The loss of effectiveness of everolimus therapy against lymphoma cells deficient in p53 function has important clinical implications,” said McArthur. “Everolimus could be a useful new string to the bow for clinicians treating patients with Myc-driven cancers, in particular B cell lymphomas, but that it would be helpful only to those patients with functional p53.”

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

New Screening Approach Identified Potential Drug Combinations for Difficult-to-treat Forms of Melanoma

registration@aacr.org () — Thu, 13 Dec 2012 12:00:00 GMT

High-throughput screen identified several drug combinations effective in vitro.
Some combinations were effective against cell lines resistant to single agent used clinically.

PHILADELPHIA — A novel approach to identifying potential anticancer drug combinations revealed that pairing cholesterol-reducing drugs called statins with cyclin-dependent kinase inhibitors might provide an effective approach to treating intractable melanomas driven by mutations in the NRAS and KRAS genes.

David F. Stern, Ph.D., professor of pathology at Yale University School of Medicine in New Haven, Conn., and colleagues reported these data in Cancer Discovery, a journal of the American Association for Cancer Research.

“The identification of gene mutations that drive specific subsets of cancers has had a major beneficial impact on treatments for these patients. But, such mutations can only be identified for some cancers. Some patients who have a specific cancer-driving genetic mutation never respond to the matching drug, while nearly all those who initially respond eventually become resistant to the effects of the drug and their cancers relapse,” said Stern.

For this reason, Stern and colleagues reasoned that using drug combinations may be necessary to address the problem of drug resistance and enable effective treatment of cancers driven by signaling molecules that currently cannot be targeted, such as RAS.

They developed an in vitro, high-throughput screen to test the effectiveness of anticancer drugs, alone and in pairs, against three types of melanoma cell lines: those driven by mutations in the RAS gene (representing approximately 20 percent of human melanomas), those driven by mutations in the BRAF gene (40 to 50 percent of melanomas) and those without mutations in either the RAS or BRAF genes.

Through analysis of 150 drugs as single agents, Stern and colleagues narrowed their pool to 40 drugs for combination testing. Melanoma cell lines driven by BRAF and RAS were sensitive to different combinations of drugs. Some combinations that killed BRAF-driven melanoma cell lines were also effective against BRAF-driven melanoma cell lines resistant to a single agent used to treat patients with melanoma tumors characterized by BRAF gene mutations, and these combinations may prove to be helpful in preventing or managing resistance to these agents.

“Perhaps the most interesting observation was that several drug combinations that included a statin, a drug class used clinically to lower cholesterol, killed RAS-driven melanoma cell lines, given the lack of success in treating such cancers,” said Stern.

One statin combination that showed efficacy in vitro, simvastatin plus flavopiridol, an inhibitor of proteins called cyclin-dependent kinases that activate cell division, also worked in vivo substantially reducing the growth of a RAS-driven human melanoma cell line transplanted into mice.

“These agents may be extremely useful as partner agents in combination therapy. Since multiple cyclin-dependent kinase inhibitors are already in human clinical trials, there may be a short path to testing the combination of a statin plus a cyclin-dependent kinase inhibitor in patients with RAS-driven melanoma,” said Stern. “There is a great need for drugs to treat cancers driven by RAS. RAS proteins are inappropriately active in up to a third of all human cancers, including melanoma and lung and pancreatic cancers.”

“This brings up the important point that our high-throughput screening approach is applicable to other types of cancer, including lung and pancreatic cancer,” he added. “A major challenge is in picking the appropriate agents for combination screening, since with multiple doses per agent, the scale of a screen needed for all combinations grows rapidly. This requires careful evaluation of single agents, and analytical methods for choosing the best candidates for follow-up in combinations. For our work, the relatively small number of genetic subtypes was very important, so this system provides a great starting point for investigation of carcinomas (lung, pancreatic cancer, breast cancer), which are genetically more complex.”

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Stand Up To Cancer and Cancer Research Institute Announce New Immunology Translational Research Dream Team

registration@aacr.org () — Wed, 12 Dec 2012 12:00:00 GMT

$10 Million Grant Over Three Years Will Fund Research Focusing on the Immunological Treatment, Control and Prevention of Cancer.

SU2C Donor, the Entrepreneur and Philanthropist Sean Parker, Contributed to Support the Immunology Dream Team.

PHILADELPHIA — Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) announce the formation of a Dream Team project dedicated to cancer immunology — “Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy.” Cancer immunology is a field of research that explores the complex relationship between cancer and the immune system, with the goal of discovering immune-based solutions to curing cancer.

The SU2C-CRI Cancer Immunology Translational Research Dream Team will receive $10 million in funding over three years for this translational cancer research project that will unite laboratory and clinical efforts leading to the immunological treatment, control and prevention of cancer.

The team will be led by James P. Allison, Ph.D., and Antoni Ribas, M.D., Ph.D. Allison is chairman of the department of immunology, director of the immunotherapy platform and co-director of the David H. Koch Center for Applied Research of Genitourinary Cancers at The University of Texas MD Anderson Cancer Center. Ribas is professor of medicine, surgery and molecular and medical pharmacology, director of the tumor immunology program area at the Jonsson Comprehensive Cancer Center, and member of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles (UCLA).

“The goal of our Dream Team is to expand, optimize and explore combinations of two novel immunotherapies, immune checkpoint blockade and adoptive T-cell transfer,” said Allison. “It is our dream, indeed our expectation, that by optimizing these two uniquely successful and complementary approaches, we will be able to achieve durable responses in a large percentage of patients suffering from a variety of types of cancer.”

“The SU2C-CRI Dream Team brings together a leading group of tumor immunologists working to speed up the pace of scientific advances to use the immune system to fight cancer,” said Ribas.

Co-leaders of the Dream Team are Drew M. Pardoll, M.D., Ph.D., and Cassian Yee, M.D. Pardoll is director of the division of immunology and Abeloff professor in the departments of oncology, medicine, pathology and molecular biology and genetics at the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University in Baltimore, Md. Yee is a member of the Clinical Research Division and program in immunology at Fred Hutchinson Cancer Research Center; a professor of medicine at the University of Washington School of Medicine; and an attending physician at the Seattle Cancer Care Alliance in Seattle, Wash.

Scientists on this Dream Team represent eight institutions: MD Anderson Cancer Center, UCLA, The Johns Hopkins University, Fred Hutchinson Cancer Research Center, Dana-Farber Cancer Institute, California Institute of Technology, Memorial Sloan-Kettering Cancer Center and the Netherlands Cancer Institute.

“The clinical advances in immunotherapy just in the past two years have shown that these strategies indeed empower the patient’s own immune system to successfully fight their cancer. Single interventions opened the door; the future is combinatorial therapy, and the synergistic expertise of our Dream Team will catalyze the development of the most innovative combinations,” said Pardoll.

“Adoptive T cell therapy in recent years has really come into its own. Novel strategies to generate long-lasting, highly effective T cells are being developed, and in combination with new immunomodulatory agents like the checkpoint inhibitors, we can fully exploit the immune system to treat patients with cancer. We are so fortunate to now have the opportunity to explore these new frontiers in immunotherapy,” said Yee.

Significant scientific developments in the field of cancer immunology and the recent FDA approvals of two cancer immunotherapies highlight the field’s potential to transform cancer treatment. The formation of this Dream Team focused on this promising area of cancer research aligns with CRI’s 60-year mission to advance cancer immunology and SU2C’s mission to accelerate the translation of scientific discovery into new treatments for cancer patients.

“Because of my deep respect for the innovative approach to cancer research taken by Stand Up To Cancer, I wanted to support the creation of a team dedicated to this emerging area of research,” said tech entrepreneur and philanthropist Sean Parker. “I am delighted that SU2C and the Cancer Research Institute have combined their expertise to select a Dream Team with such great potential to move the field forward through cutting-edge technology and science.”

“Cancer immunology, a field which the Cancer Research Institute pioneered and has led for sixty years, is a high-potential area of medical research that is producing some of today’s greatest breakthroughs in cancer patient treatment, and I am confident that this Dream Team is going to succeed in making the next great advance,” said Jill O’Donnell-Tormey, Ph.D., chief executive officer and director of scientific affairs at CRI.

“Stand Up To Cancer is excited to make this investment in exploring strategies that can activate and enhance the body’s own natural ability to fight cancer. The field of cancer immunology is ripe with possible breakthroughs that could change the landscape of cancer treatment, and thus perfectly suited to Stand Up To Cancer’s mission to accelerate research that can make more cancer patients survivors,” said Sherry Lansing, SU2C co-founder, founder of the Sherry Lansing Foundation, and chairperson of the Entertainment Industry Foundation’s (EIF) Board of Directors. (SU2C is a program of EIF, which is a 501(c)3 charitable organization.)

“Along with collaboration, innovation is a pillar of SU2C’s model of cancer research, and we are incredibly grateful to have the support of a true innovator in the world of technology like Sean Parker,” said SU2C Co-founder Rusty Robertson. “With this immunology-focused Dream Team, we have the opportunity to utilize Sean Parker’s generous contribution to advance a cutting-edge field that holds great potential to save lives.”

The SU2C-CRI Cancer Immunology Translational Research Project

Cancer immunologists have long hypothesized that specific interventions could stimulate and “re-educate” patients’ own immune systems to attack their cancer. In one immunology-based cancer treatment approach, what kills cancer cells is a type of white blood cell called the T lymphocyte. Expanding these T lymphocytes outside the body, engineering them to be more potent and reinfusing these souped up anti-cancer lymphocytes into patients – a process termed adoptive cell therapy or ACT – is like adding more soldiers to the immune army. However, lymphocytes also have inhibitory receptors, termed checkpoints, that put the brakes on immune responses. Cancers exploit these checkpoints to resist immune attack by the anti-tumor lymphocytes. Blocking checkpoints with specific antibodies disables the brake and allows the immune system to get the upper hand.

The Dream Team will focus on two approaches to overcome these obstacles. First, they will investigate checkpoint blockade, where the checkpoints themselves are inhibited using antibodies, once again allowing T lymphocytes to kill the cancer cells. Second, the team will pursue multiple ACT approaches.

Using tumors obtained from patients, the team will evaluate checkpoint expression before and after ACT and/or checkpoint blockade, and will test the hypothesis that multiple T lymphocyte targets are generated in the tumor. The clinical impact of this project lies with the potential synergy of combining these two immunology-based therapeutic approaches to treat a range of tumor types to improve the lives of patients with cancer.

The project is estimated to start in the spring of 2013, with the first clinical trials scheduled to open in early 2014.

Dream Team Selected Through Unique, Rigorous Process

A SU2C-CRI Joint Scientific Advisory Committee (JSAC) conducted a unique, interactive, rapid and rigorous evaluation of the applications using a multi-step scientific review process. The JSAC is composed of highly accomplished senior laboratory researchers and physician-scientists, as well as patient advocates.

The committee is chaired by Nobel laureate Phillip A. Sharp, Ph.D., institute professor at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. It is co-chaired by Giorgio Trinchieri, M.D., and Carl H. June, M.D. Trinchieri is director of the Cancer and Inflammation Program and chief of the Laboratory of Experimental Immunology at the Center for Cancer Research, National Cancer Institute, and associate director for basic science at the Trans-NIH Center for Human Immunology. June is director of translational research at the Abramson Cancer Center at the University of Pennsylvania, and is an investigator with the Abramson Family Cancer Research Institute. He is also a professor in the department of pathology and laboratory medicine.

The review process began with a call for letters of intent in March of 2012 by the American Association for Cancer Research (AACR), SU2C’s scientific partner. The committee then chose four finalist teams, each of which met in person with the JSAC to present plans for their research and respond to questions about their projects – a level of interaction between applicants and reviewers that is unique among scientific review processes.

The AACR is responsible for administering the grant and provides ongoing scientific oversight to ensure that progress is being made. Since the launch of Stand Up To Cancer, the AACR has played an integral role as SU2C’s scientific partner by providing scientific leadership, expert peer review and grants administration.

Dream Team Principals and Advocate Members

The “Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy” Dream Team consists of a multidisciplinary group of experts that includes laboratory and clinical researchers, young investigators and senior scientists who have not worked together in the past, as well as patient advocates. Besides Allison, Ribas, Pardoll and Yee, team members include:

Principals:

David Baltimore, Ph.D., California Institute of Technology, Pasadena, Calif.
Glenn Dranoff, M.D., Dana-Farber Cancer Institute, Boston, Mass.
Philip D. Greenberg, M.D., Fred Hutchinson Cancer Research Center, Seattle, Wash.
Michel Sadelain, M.D., Ph.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Ton Schumacher, Ph.D., Netherlands Cancer Institute, Amsterdam, The Netherlands
Jedd D. Wolchok, M.D., Ph.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y.

Advocates:

Robert E. Behrens, REB Investments Inc.
Debra Black, Melanoma Research Alliance
Roy Doumani, cancer survivor
Valerie Guild, Aim at Melanoma
Jonathan W. Simons, M.D., Prostate Cancer Foundation
Mary Elizabeth Williams, Salon.com

A video with more information about this new dream team is available at bit.ly/12jHPpa.

Since Stand Up To Cancer’s launch in 2008, SU2C has awarded grants to nine Dream Teams and one International Translational Cancer Research Grant. Twenty-six Innovative Research Grants have been awarded to individual young investigators. These recipients comprise more than 450 scientists from 87 institutions.

# # #

About Stand Up To Cancer
Stand Up To Cancer (SU2C) — a program of the Entertainment Industry Foundation (EIF), a 501(c)3 charitable organization — raises funds to hasten the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. In the fall of 2007, a group of women whose lives have all been affected by cancer in profound ways began working together to marshal the resources of the media and entertainment industries in the fight against this disease.

Members of the SU2C Executive Leadership Council (ELC) include Talk Show Host, Journalist and well-known Cancer Advocate Katie Couric; Sherry Lansing, Chairperson of the Entertainment Industry Foundation’s Board of Directors and founder of the Sherry Lansing Foundation; EIF President and CEO Lisa Paulsen; EIF Senior Vice President Kathleen Lobb; Rusty Robertson and Sue Schwartz of the Robertson Schwartz Agency; Pamela Oas Williams, President of Laura Ziskin Productions and Executive Producer of Stand Up To Cancer’s In-House Production Team, and Nonprofit Executive Ellen Ziffren. All of the ELC members were co-producers of the 2012 televised special. The late Laura Ziskin, executive producer of both the Sept. 5, 2008 and Sept. 10, 2010 broadcasts, was also a member of the ELC. SU2C was formally launched on May 27, 2008. Sung Poblete, Ph.D., R.N., has served as SU2C’s president and CEO since 2011.

SU2C’s “Dream Team” approach to funding translational cancer research enables scientists from different disciplines at research centers across the country and internationally to collaborate on projects geared toward getting new, less toxic treatments to patients as quickly as possible. Monies also support innovative cancer research projects that are often deemed “too risky” by conventional funding sources. Sixty-five institutions are currently involved. As SU2C’s scientific collaborator, the American Association for Cancer Research, led by a prestigious SU2C Scientific Advisory Committee, provides scientific oversight, expert review of the research projects and grants administration. For more information, visit standup2cancer.org.

About the Cancer Research Institute
The Cancer Research Institute (CRI), a nonprofit established in 1953, is the global leader in cancer immunology. Since its inception, CRI has invested hundreds of millions of dollars to support research conducted by more than 3,000 scientists and clinicians worldwide to understand the immune system and how it can be harnessed to conquer all cancers. This work has laid the foundation for nearly every major cancer immunotherapy breakthrough over the past half century.

Guided by an international panel of the world’s leading immunologists and cancer immunologists, including three Nobel laureates and 29 members of the U.S. National Academy of Sciences, CRI provides essential funding to support every stage of discovery, from laboratory investigation to clinical trials of the most promising cancer immunotherapies for patients.
CRI also sponsors a seminal international symposium on cancer immunology each year, hosts annual scientific colloquia dedicated to overcoming challenges in immunotherapy research and development, forges collaborative partnerships between academia and industry to facilitate the development pathway for novel immunotherapeutics, and presents special recognition awards to individuals who have made outstanding contributions to cancer research, patient care and public awareness.

Through its sustaining support and leadership in the field, CRI is accelerating the development of safe and effective immunotherapies that stand to revolutionize the treatment of all cancers. For more information, visit http://cancerresearch.org or follow CRI on Twitter @CancerResearch.

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional association dedicated to advancing cancer research and preventing and curing cancer. AACR membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org. Follow the AACR on Twitter: @aacr #aacr. Follow the AACR on Facebook: http://www.facebook.com/aacr.org.

Media Contacts:

SU2C
Adam Pockriss
(212) 843-8286
apockriss@rubenstein.com

CRI
Brian Brewer
(917) 676-0871
bbrewer@cancerresearch.org

AACR
Rick Buck
(215) 446-7162
Rick.Buck@aacr.org

Obesity and Overeating During Menopause Together Promote Breast Tumor Growth and Progression

registration@aacr.org () — Fri, 07 Dec 2012 12:00:00 GMT

In a rat model, premenopausal obesity impaired ability to handle postmenopausal overeating.
Obese animals’ tumors expressed more markers of increased energy use and proliferation.
Results have implications for weight and metabolic control in perimenopausal women.

PHILADELPHIA — Obese women might be able to eliminate their increased risk for postmenopausal breast cancer by taking measures during perimenopause to prevent weight gain and to therapeutically control the metabolic effects of their obesity, according to the results of a preclinical study published in Cancer Research, a journal of the American Association for Cancer Research.

“Obese postmenopausal women have increased risk for breast cancer and poorer clinical outcomes compared with postmenopausal women who are lean,” said Paul S. MacLean, Ph.D., associate professor of medicine at the University of Colorado Anschutz Health and Wellness Center in Aurora, Colo. “The reasons for this are not fully understood.

“Unfortunately you cannot do the studies needed to address this issue in humans. So, we merged rat models of obesity, breast cancer and menopause to best mimic the events that link premenopausal obesity to an increased rate of postmenopausal breast cancer.”

During menopause, women often gain weight because they consume more food than their body needs. In a previous study, MacLean and colleagues used their rat model to show that weight gain following surgical ovariectomy, which models menopause, helped promote breast tumor development in obese rats.

In this study, they confirmed that obesity and overfeeding after surgical ovariectomy together drove aggressive tumor growth and progression.

One reason was that obese rats were unable to appropriately handle the excess sources of energy, in the form of glucose and dietary fat, which accumulated as a result of overfeeding after surgical ovariectomy. Lean rats stored the excess glucose and dietary fat from overfeeding in liver, fat, muscle and healthy breast tissue, a normal metabolic response to overfeeding. In contrast, the healthy tissues in obese rats failed to increase uptake of glucose and dietary fat, but the breast tumors dramatically increased uptake of glucose.

A second reason for the enhanced tumor growth and progression in obese rats compared with lean rats was that tumors from the two groups of animals had different molecular profiles. Tumors from obese rats had higher levels of expression of the progesterone receptor (PR), which was related to higher expression of genes involved in energy use and proliferation.

A similar pattern of increased expression of genes involved in energy use and cell growth was seen in human PR-positive breast tumors from postmenopausal women. According to MacLean, a final piece of evidence indicating that obesity and overfeeding during the menopausal transition converge to promote tumor growth and progression was that the antidiabetic drug metformin reduced tumor burden in obese rats after surgical ovariectomy.

“If our findings in rats translate to humans, it means that the perimenopausal period is a critical window of time for determining breast cancer risk later in life,” said MacLean. “This, in turn, means that an obese woman’s risk for postmenopausal breast cancer and poor clinical outcome could be reduced by perimenopausal lifestyle modifications, such as restricting food consumption and increasing exercise, and/or perimenopausal use of drugs, such as metformin, to improve metabolic control.”

MacLean and colleagues are now testing this hypothesis in the rat model.

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Extending Adjuvant Trastuzumab Treatment Time Provided No Additional Benefit

registration@aacr.org () — Fri, 07 Dec 2012 12:00:00 GMT

High number of patients who received one year of trastuzumab were disease-free eight years later.
One year of trastuzumab showed superior safety profile with no major cardiac toxicity.
Efficacy of two years of trastuzumab treatment was comparable to one year.

SAN ANTONIO — One year of adjuvant trastuzumab should remain the standard of care for patients with HER2-postive early-stage breast cancer, according to data from the phase III HERA trial, which compared the efficacy and safety of one year and two years of treatment.

“Giving trastuzumab for a longer duration (two years) did not improve disease-free or overall survival compared with one year of trastuzumab treatment,” said Martine J. Piccart, M.D., Ph.D., chief of the medicine department at the Jules Bordet Institute in Brussels, Belgium, president of the European Society for Medical Oncology and chair of the Breast International Group (BIG). Piccart presented these data at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

Piccart and colleagues took part in the HERA trial, an international, multicenter, phase III, randomized trial run by BIG and Roche that spanned several countries. They followed 5,102 women with HER2-positive early-stage breast cancer randomly assigned to trastuzumab every three weeks for one year or two years, or to observation. All women completed primary therapy of surgery, chemotherapy and radiotherapy as indicated.

Disease-free status and overall survival rates were comparable between the one- and two-year trastuzumab arms. In addition, while the primary cardiac endpoint of symptomatic congestive heart failure was comparable in both arms, the secondary cardiac endpoint of asymptomatic cardiac dysfunction was higher in the two-year arm, at 7.2 percent compared with 4.1 percent in the one-year arm. Most of the cardiac events occurred during trastuzumab administration, and the majority were reversible when the trastuzumab was stopped.

“The HERA trial showed the sustainability of the efficacy of trastuzumab, proving that a significant proportion of patients treated with trastuzumab in the adjuvant setting are alive and free of disease recurrence after a median follow-up of eight years,” Piccart said. “It is also reassuring with regard to the low cardiac toxicity of trastuzumab when given after adjuvant chemotherapy. Finally, it confirms that one year of adjuvant trastuzumab should remain the standard of care in women with HER2-positive early breast cancer.”

# # #

The mission of the 2012 CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR’s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit www.sabcs.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In San Antonio, Dec. 4-8:
(210) 582-7035

Breast Cancer Genome Sequencing Identified HER2 Mutations as Targets for Drug Treatment

registration@aacr.org () — Fri, 07 Dec 2012 12:00:00 GMT

HER2 mutations occurred separately from HER2 gene amplification and DNA sequencing is required to detect them.
HER2 mutations are rare but can be immediately treated with existing drugs.
Phase II study using neratinib to treat HER2 mutations is under way.

SAN ANTONIO — An analysis of data from a series of studies documenting breast cancer genome sequencing has confirmed that HER2 mutations may be ideal targets for breast cancer treatment. Further, the majority of these mutations are activating mutations that drive breast cancer cell growth in tissue culture.

Ron Bose, M.D., Ph.D., assistant professor in the division of oncology at the Washington University School of Medicine and the Siteman Cancer Center in St. Louis, Mo., presented these results at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8. The data were also published in Cancer Discovery, a journal of the American Association for Cancer Research.

Bose and colleagues reviewed data from eight genome-sequencing studies that included nearly 1,500 patients. Twenty-five patients’ cancer had HER2 mutations, nearly all of which occurred in those who did not have HER2 gene amplification, the hallmark of HER2-positive breast cancer. Bose estimated that HER2 mutations occur in 1 percent to 2 percent of breast cancer cases, but there may be subgroups in which the frequency of this mutation is higher.

“Normally, patients with HER2 mutations would not qualify to receive drugs that target HER2, such as trastuzumab, because the HER2 gene amplification tests will come back as normal. This is because the current testing used to measure HER2 in breast cancer will not pick up HER2 mutations. DNA sequencing of HER2 is needed,” Bose said. “It is possible that patients with cancers containing HER2 mutations will benefit from receiving the same drugs that are currently used to treat patients with HER2-positive breast cancer.”

Analysis showed that HER2 mutations clustered in two regions of the HER2 gene. The researchers found one cluster in 20 percent of patients in the outside half of HER2, called the extracellular domain. Seventy percent of patients had mutations in the inside half of HER2, specifically in the tyrosine kinase domain. After testing 13 HER2 mutations, the researchers found a majority were activating mutations that were sensitive to the drugs lapatinib and trastuzumab. Two of the mutations, however, were resistant to lapatinib and sensitive to neratinib.

“The activating mutations are turning on HER2’s functioning and will probably result in abnormal, unregulated HER2 signaling, which is likely driving the cancer cell,” Bose said. “These mutations were sensitive to HER2 tyrosine kinase inhibitors. Many were sensitive to lapatinib, an FDA-approved drug, and all were sensitive to neratinib, a drug in phase II clinical trials.”

However, not all HER2 mutations were activating mutations. A few mutations appeared to be “silent events” occurring in the genome of the cancer. “Just because we see a mutation in the HER2 gene does not guarantee that every case is an activating mutation that is sensitive to drugs,” Bose said. “The best way to find out is to test individual mutations in the laboratory.”

Bose and his colleagues are now working on a multicenter, phase II clinical trial testing neratinib in patients who have HER2 mutations in their breast cancer.

# # #

Phase III Trial Did Not Show Superiority of Eribulin Compared With Capecitabine in Metastatic Breast Cancer

registration@aacr.org () — Fri, 07 Dec 2012 12:00:00 GMT

Eribulin showed trend toward improved overall survival versus capecitabine.
Eribulin showed greater activity in certain subsets of patients.
Researchers are still gathering quality-of-life data.

SAN ANTONIO — A phase III multicenter study of eribulin mesylate in women with previously treated metastatic breast cancer failed to meet its co-primary endpoints of improved progression-free survival and overall survival compared with capecitabine, according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

“The study did not show a statistically significant benefit of eribulin over capecitabine, and it did not show a benefit in terms of progression-free survival, so the overall study objectives were not met,” said Peter A. Kaufman, M.D., associate professor of medicine at the Geisel School of Medicine at Dartmouth and the Norris Cotton Cancer Center in Lebanon, N.H.

“However, this is the first study demonstrating that eribulin is active in the first-, second- and third-line setting in metastatic breast cancer,” Kaufman said. “Although we didn’t show a statistically significant superiority over capecitabine, which was our goal, numerically the overall survival with eribulin was better than with capecitabine.”

In 2010, the FDA approved eribulin for the treatment of patients with metastatic breast cancer who had previously received an anthracycline and a taxane and at least two cytotoxic chemotherapy treatment regimens for metastatic breast cancer. The FDA granted approval based on data showing a statistically significant improvement in overall survival compared with current treatments.

Kaufman and colleagues examined whether eribulin would be effective as an earlier-line treatment in women with metastatic breast cancer. They randomly assigned 1,102 patients to eribulin or capecitabine. Patients had all received prior anthracycline- and taxane-based therapy and received the study drug as the first, second or third line of therapy for metastatic disease.

The median overall survival for patients assigned to eribulin was 15.9 months compared with 14.5 months for patients assigned to capecitabine. Median progression-free survival was 4.1 months for eribulin and 4.2 months for capecitabine.

Exploratory analyses of patient subsets showed that the median overall survival in women with HER2-negative breast cancer was 15.9 months with eribulin compared with 13.5 months with capecitabine. In women with triple-negative breast cancer, which is a particularly aggressive subset, the median overall survival was 14.4 months with eribulin compared with 9.4 months with capecitabine.

Kaufman and colleagues are still compiling data from the quality-of-life analysis, which according to Kaufman, will help guide their next steps in further studying eribulin in this patient population.

“Although we did not meet our primary endpoints, this is still the first study demonstrating the activity of eribulin in earlier lines of treatment of metastatic breast cancer,” Kaufman said. “Eribulin is an active therapy in this setting, and overall, it has potentially comparable activity to capecitabine, which is a widely used treatment in this patient population.”

# # #

Adjuvant Bevacizumab Did Not Improve Invasive Disease-free Survival in Triple-negative Breast Cancer

registration@aacr.org () — Fri, 07 Dec 2012 12:00:00 GMT

Safety profile was consistent with previous trials of bevacizumab.
More understanding of triple-negative breast cancer is still needed.
Final overall survival data are expected in 2013.

SAN ANTONIO — Patients who received one year of bevacizumab in addition to chemotherapy for the postsurgical treatment of triple-negative breast cancer had no statistically significant improvement in invasive disease-free survival compared with patients treated with chemotherapy alone, according to the primary results of the phase III BEATRICE study.

“This study did not confirm the hypothesis that adding bevacizumab to chemotherapy would improve patients’ outcomes,” said David Cameron, M.D., professor of oncology at Edinburgh University in Scotland, who presented the results at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8. “Therefore, sadly for patients, we have nothing extra to add to chemotherapy for early, triple-negative breast cancer.”

Prior research has shown that bevacizumab combined with chemotherapy significantly improves progression-free survival in metastatic breast cancer and improves pathologic complete response in the neoadjuvant setting. The dependence of micrometastases on angiogenesis suggested to Cameron and his colleagues that patients might benefit from anti-angiogenic strategies, such as bevacizumab, applied in the adjuvant setting.

In BEATRICE, an open-label, multinational, phase III study, researchers randomly assigned 2,591 patients with triple-negative operable primary invasive breast cancer to four or more cycles of anthracycline-based or taxane-based chemotherapy with or without one year of bevacizumab.

At a median follow-up of 32 months, the hazard ratio for invasive disease-free survival was 0.87 (95% CI 0.72–1.07) in favor of patients assigned to chemotherapy and bevacizumab. Researchers reported 107 deaths among patients who received chemotherapy alone compared with 93 deaths among those who received chemotherapy and bevacizumab.

“The findings are reminiscent of what was reported in operable colorectal cancer,” Cameron said. “Bevacizumab clearly does something in this setting, but the effect is not sustained, and therefore, adding bevacizumab to chemotherapy for all these patients is not the way to improve their chances.”

Researchers found no difference in the amount of chemotherapy delivered and found no increase in the risk for fatal adverse events in patients assigned to bevacizumab. However, the addition of bevacizumab to chemotherapy was associated with an increase in grade 3 or worse hypertension, left ventricular dysfunction and congestive heart failure.

“We still need to understand what is special about the biology of breast cancers that do not express hormone receptors, nor overexpress HER2,” Cameron said. “We need to explore which cancers might benefit from other additional therapies, including the possibility that some of them might benefit from drugs like bevacizumab.”

# # #

Cognitive Problems May Be Present Before Chemotherapy in Women With Breast Cancer

registration@aacr.org () — Fri, 07 Dec 2012 12:00:00 GMT

“Chemo brain” may be an inaccurate descriptor of cognitive issues.
Fatigue is a key contributor to cognitive problems.
Interventions to reduce stress and fatigue may alleviate postchemotherapy neurocognitive problems.

SAN ANTONIO — Women undergoing chemotherapy who experience cognitive problems, commonly referred to as “chemo brain,” displayed alterations in neurocognitive responses prior to undergoing treatment, according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

Bernadine Cimprich, Ph.D., R.N., associate professor emerita at the University of Michigan School of Nursing in Ann Arbor, and colleagues found that pretreatment neurocognitive compromise and fatigue were key contributors to the cognitive effects often attributed to chemotherapy.

“For a long time, women undergoing treatment for breast cancer have reported cognitive problems such as trouble thinking clearly, remembering things, and carrying out jobs and other responsibilities, which we have attributed to chemotherapy or ‘chemo brain,’” Cimprich said. “Research shows that these problems do occur in some women during chemotherapy, but we still do not understand what the underlying causes are.”

Cimprich and her colleagues reasoned that the mental demand and stress of a breast cancer diagnosis could play a role in these early cognitive problems. They tested neurocognitive responses using functional magnetic resonance imaging (fMRI) on 28 women who received adjuvant chemotherapy, 37 who received radiotherapy and 32 healthy controls. Before treatment and one month after treatment, the participants performed a verbal working memory task with varying levels of demand for cognitive control during fMRI scanning. They also provided self-reports of fatigue.

Women who underwent chemotherapy reported a significantly higher level of fatigue and performed less accurately on the cognitive tests before treatment and one month after treatment. In addition, greater fatigue correlated with poorer test performance and more cognitive problems reported over time.

Brain imaging before treatment showed reduced function in regions needed to perform the task in both patient groups when compared with controls, with more compromise seen in women awaiting chemotherapy. Women who were less successful in recruiting the brain regions needed for the task before treatment were more likely to suffer greater fatigue over time, regardless of treatment group.

“Our initial findings showed that the level of worry interfered with patients’ ability to do a task,” Cimprich said. “The level of worry had a key role in the cognitive problems with these women before treatment, and this worry was related to fatigue.”

Scores for cognitive testing from women who underwent radiation treatment fell between those of women who underwent chemotherapy and those of the healthy women.

“Women faced with the decision to undergo chemotherapy should know that cognitive problems, should they occur, may not always stem from chemotherapy,” Cimprich said. “Women should not avoid accepting recommendations for lifesaving chemotherapy for fear of ‘chemo brain.’”

Cimprich recommended existing interventions to combat stress after a breast cancer diagnosis, including mindfulness intervention, psychological support, cognitive behavior interventions and exercise.

“It might be possible to diminish worry and fatigue and maintain strong brain function during the course of treatment using these interventions,” Cimprich said.

The research was funded by the National Institutes of Health.

# # #

Chemotherapy After Complete Surgical Removal of Local or Regional Breast Cancer Recurrence Increased Survival Rates

registration@aacr.org () — Thu, 06 Dec 2012 12:00:00 GMT

Disease-free and overall survival improved with postsurgical chemotherapy.
Patients with ER-negative breast cancers were most responsive to treatment.

SAN ANTONIO — Chemotherapy after surgery, or adjuvant chemotherapy, led to higher rates of disease-free and overall survival for women with isolated local or regional recurrence of breast cancer, according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

Patients with isolated local and/or regional recurrence of their breast cancers are at high risk for developing metastases in other areas of the body. Some physicians administer chemotherapy to these patients after their recurrent tumors have been completely removed by surgery, but the efficacy of this treatment had not been studied until now.

“This is the first randomized controlled study that shows that adjuvant chemotherapy works in these patients,” said Stefan Aebi, M.D., head of the division of medical oncology at Luzerner Kantonsspital in Luzern, Switzerland.

He and his colleagues from the Breast International Group, the National Surgical Adjuvant Breast and Bowel Project and the International Breast Cancer Study Group evaluated 162 patients with isolated local and regional recurrence; 85 received adjuvant chemotherapy and 77 did not.

Five-year disease-free survival rates were 69 percent for women who received adjuvant chemotherapy and 57 percent for those who did not. The overall survival rate was 88 percent for women who received chemotherapy compared with 76 percent for those who did not.

Women with estrogen receptor (ER)-negative breast cancer demonstrated the greatest benefit, with a five-year disease-free survival rate of 67 percent among those who received chemotherapy versus 35 percent among those who did not. In addition, within this group, overall survival rates were 79 percent among those who received chemotherapy and 69 percent among those who did not.

For patients with ER-positive disease, five-year disease-free survival was 70 percent for those who received chemotherapy versus 69 percent for those who did not. Overall survival was 94 percent for those patients with ER-positive disease who received chemotherapy versus 80 percent among those who did not.

Aebi recommended that physicians prescribe adjuvant chemotherapy for patients with isolated local and regional recurrence of breast cancer, especially if the recurrence is ER-negative and therefore not sensitive to endocrine therapy.

This research was funded by the National Cancer Institute, the Swiss Cancer League and other national cancer research agencies.

# # #

Diverse Genetic Alterations Found in Triple-negative Breast Cancers After Neoadjuvant Chemotherapy

registration@aacr.org () — Thu, 06 Dec 2012 12:00:00 GMT

Residual tumor cells are found in up to 70 percent of these patients.
Multiple types of potentially actionable somatic genetic changes in the residual cancer remain in the breast after treatment.
Molecular information from the tumor remaining after neoadjuvant therapy could lead to targeted therapies postsurgery.

SAN ANTONIO — Many different genetic alterations were detected in tumor cells left behind after patients with triple-negative breast cancer were treated with chemotherapy prior to surgery (neoadjuvant chemotherapy), according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8. The investigators hope this knowledge will help move toward early personalized treatment to combat this aggressive subtype of breast cancer.

“The standard of care for many patients with triple-negative breast cancer is to administer chemotherapy before surgery to shrink the tumor,” said Justin M. Balko, Pharm.D, Ph.D., research faculty who led this study in the laboratory of Carlos Arteaga, M.D., at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

“Unfortunately, about 70 percent of patients still have some residual disease at the time of surgery, despite treatment,” Balko said. “We speculate this residual disease in the breast should look just like simultaneous micrometastases that are destined to recur in the same patient. Thus, we need to know what is in this tissue that is left behind to conceive targeted therapies to treat and prevent recurrence of metastases down the road.”

Balko and colleagues profiled residual tumor tissue from 102 patients with triple-negative breast cancer who had received neoadjuvant chemotherapy. In DNA from 89 evaluable tumors, the investigators used deep sequencing to examine 182 oncogenes and tumor suppressors that are known to be altered in human cancers. Instead of finding similar genes affected among the patients, they found a diverse set of genes were altered.

“We already knew that triple-negative breast cancer is driven by a diverse group of genetic alterations,” said Balko. “So, in one way, we fell further down this rabbit hole, but we also found some things that could be promising therapeutically, such as frequent MYC, MCL1 and JAK2 amplifications as well as mutations in the PI3K pathway.”

According to Balko, the next step is to confirm the findings in a larger patient cohort, and if the findings are replicated, broad molecular approaches will be needed to help inform personalized therapies for triple-negative breast cancer. Furthermore, it will be necessary to explore the therapeutic sensitivity of breast cancers harboring these lesions in the laboratory to know how to treat patients with breast cancer who have these alterations.

This research was a collaboration of the Breast Cancer Research Program at Vanderbilt, the Instituto Nacional de Enfermedades Neoplásicas (Lima, Perú) and Foundation Medicine (Cambridge, Mass.). It was funded by the Susan G. Komen for the Cure Foundation, the National Institutes of Health (Vanderbilt Breast SPORE Grant P50 CA98131) and the Lee Jeans/Entertainment Industry Foundation Translational Breast Cancer Research Program.

# # #

The mission of the CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR’s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit www.sabcs.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In San Antonio, Dec 4-8:
(210) 582-7035

HDAC Inhibitors Sensitized Triple-negative Breast Cancer Cells to PARP Inhibition and Cisplatin Treatment

registration@aacr.org () — Thu, 06 Dec 2012 12:00:00 GMT

HDAC inhibitors indirectly caused DNA damage and impaired DNA repair.
Cellular conditions created by HDAC inhibition mimicked those in BRCA1-mutated breast cancer cells.
Findings could have implications for hard-to-treat triple-negative breast cancer.

SAN ANTONIO — In-vitro exposure to an HDAC inhibitor indirectly impaired the ability of triple-negative breast cancer cells to repair damaged DNA and sensitized the cells to treatment with two therapies that have clinical activity in some patients with breast cancer — a PARP inhibitor and cisplatin, according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

“Triple-negative breast cancer is a particularly aggressive breast cancer that is not susceptible to traditional hormone therapies,” said Kapil N. Bhalla, M.D., chief of personalized cancer medicine at the University of Kansas Cancer Center in Kansas City. “That is why it is important to try to find new ways of killing triple-negative breast cancer cells.”

Cells of certain human tumors rely on intact DNA repair pathways for survival. Prior research has shown that proteins such as ATR, CHK1 and BRCA1 are essential parts of a cell’s response to DNA damage and its subsequent repair of the damage. These three proteins are controlled or chaperoned by heat shock protein 90 (hsp90).

Bhalla and colleagues previously found that treatment with an HDAC inhibitor renders hsp90 inactive, thus impeding the DNA damage response that involves the ATR, CHK1 and BRCA1 proteins. Therefore, HDAC inhibition creates an environment within cells that is similar to that seen in breast cancer cells with BRCA1 mutations.

“In simple terms, we are trying to cause a ‘BRCAness’ so that you confer on triple-negative breast cancer cells the sensitivity to PARP inhibitors or platinum therapy seen when BRCA1 mutations are present,” Bhalla said.

The researchers examined the mechanism of action of HDAC inhibitors and determined that inhibition of HDAC3 specifically rendered hsp90 inactive and consequently inhibited repair of damaged DNA.

“The icing on the cake, so to speak, was that in addition to inhibiting the DNA damage response through depletion of DNA repair proteins, HDAC inhibitors induced DNA damage,” Bhalla said. “By using HDAC inhibitors, we were targeting the cancer two ways at once.”

The researchers also tested whether treatment with the HDAC inhibitors vorinostat or panobinostat would sensitize triple-negative breast cancer cells to PARP inhibition. Combined treatment with either of the HDAC inhibitors plus the PARP inhibitor ABT888 resulted in the death of triple-negative breast cancer cells with or without BRCA1 mutation. In addition, vorinostat treatment made the triple-negative breast cancer cells more susceptible to treatment with cisplatin.

If further validated, the findings of this study could have implications for women with triple-negative breast cancer and possibly even women with ovarian cancer, which has a genetic makeup similar to that of triple-negative breast cancer, according to Bhalla.

“If you have a patient with triple-negative breast cancer who does not have a BRCA1 mutation, you could consider a clinical trial using an HDAC inhibitor in combination with a PARP inhibitor and cisplatin,” Bhalla said.

Bhalla has received clinical research support from Novartis Oncology, which makes panobinostat, the HDAC inhibitor used in the studies.

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Young Women With Breast Cancer Were More Likely Than Older Women to Respond to Neoadjuvant Chemotherapy

registration@aacr.org () — Thu, 06 Dec 2012 12:00:00 GMT

Finding was confined to those with triple-negative and luminal-type breast cancer.
Better outcomes seen for young women with luminal A-like tumors who achieved a pathological complete response compared with those who did not.
Neoadjuvant chemotherapy needed for young women, even those with HR-positive, HER2-negative disease.

SAN ANTONIO — Women with breast cancer aged 35 or younger were more likely than older women to achieve a pathological complete response after neoadjuvant chemotherapy, according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

“Young women with breast cancer are rare, and some data indicate that their prognosis is worse than it is for older women,” said Sibylle Loibl, M.D., Ph.D., an associate professor at the University of Frankfurt in Germany. “This is not only because their tumors tend to be more aggressive, but because breast tumors that arise in women who are young seem to be a special biological entity.”

Loibl and colleagues evaluated data from eight German studies that included 8,949 women with operable or locally advanced, nonmetastatic breast cancer who were treated with neoadjuvant chemotherapy. The researchers compared pathological complete response and disease-free survival for the subgroup of 704 women aged 35 or younger to those of older women. The subgroup of younger women included a greater proportion of triple-negative breast cancer cases and a smaller proportion of luminal A-type breast cancer cases than in the group of women aged older than 35 (26 percent versus 19 percent and 21 percent versus 27 percent for triple-negative and luminal A-type, respectively).

The pathological complete response rate was significantly higher in very young women — 23.6 percent compared with 15.7 percent among older women. Through further analysis, the researchers found this difference was isolated to women with triple-negative breast cancer and luminal-like breast cancer.

They found no difference in disease-free survival according to age among those patients who achieved a pathological complete response. However, disease-free survival was significantly worse among young women who did not achieve a pathological complete response.

In addition, tumor biology seemed to play an important role, especially in young women, for predicting pathological complete response and survival, according to Loibl. Age, but not pathological complete response, predicted disease-free survival in women with luminal A-type cancer. However, the worst disease-free survival rate was among women with this type of cancer who were younger than 35 and did not achieve a pathological complete response. The best disease-free survival rate was among women younger than 35 who did achieve a pathological complete response.

“The most surprising finding was that young women with a luminal-type tumor — hormone receptor-positive and HER2-negative — who achieved a pathological complete response had a better survival rate than the patients with nonpathological complete response,” Loibl said. “This is not true for other age groups, which indicates that breast cancer in the young — even when a luminal-type breast cancer — is chemosensitive.”

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Hypofractionated Radiotherapy Was Safe, Effective for Early Breast Cancer Treatment at 10-year Follow-up

registration@aacr.org () — Thu, 06 Dec 2012 12:00:00 GMT

Low local relapse rates were observed after breast cancer radiotherapy.
Lower total radiation dose in fewer, larger fractions was effective.
Three-week, 15-fraction schedule is the standard of care in the United Kingdom.

SAN ANTONIO — Appropriately dosed hypofractionated radiotherapy was gentle on healthy tissues and effective in controlling local-regional early breast cancer, according to 10-year follow-up results from the U.K. Standardization of Breast Radiotherapy Trials (START), presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

“Long-term follow-up confirms that a lower total dose of radiation in fewer, slightly larger fractions delivered over a shorter treatment time is at least as safe and effective as standard five-week schedules of curative radiotherapy in women with early breast cancer,” said John Yarnold, M.B.B.S., professor of clinical oncology at The Institute of Cancer Research in London and honorary consultant at The Royal Marsden NHS Foundation Trust.

Between 1999 and 2002, 4,451 women with completely excised invasive breast cancer were recruited to either the START A or START B randomized controlled trials. In START A, researchers compared 50 Gy of postsurgery radiotherapy given in 25 fractions for five weeks versus 41.6 Gy or 39 Gy in 13 fractions for five weeks. In START B, they compared 50 Gy in 25 fractions for five weeks versus 40 Gy in 15 fractions for three weeks.

Data revealed 139 local-regional tumor relapses among the 2,236 women in START A who were followed for an average of 9.3 years and 95 local-regional relapses in the 2,215 women in START B, followed for an average of 9.9 years.

The 10-year local-regional relapse rates for START A were 7.4 percent after 50 Gy, 6.3 percent after 41.6 Gy and 8.8 percent after 39 Gy. In previously published data from START B, the 10-year local-regional relapse rate was 5.5 percent after 50 Gy and 4.3 percent after 40 Gy.

“These long-term data from the START A trial confirm the findings of our earlier results that breast cancer is, on average, as sensitive to the radiation dose of each fraction as the dose-limiting normal tissues of the breast area and that this effect persists for at least 10 years,” Yarnold said.

However, a five-week, 13-fraction schedule does not offer shortened overall treatment times. “Hence, we also designed the START B trial, a pragmatic comparison of three-week and standard five-week schedules, testing for noninferiority,” said Yarnold. “The 15-fraction schedule is definitely gentler on the healthy tissues, and these long-term data confirm our earlier findings that it appears noninferior in terms of tumor control — a very favorable result.”

The three-week, 15-fraction schedule is now the standard of care in the United Kingdom and is becoming increasingly more common in other countries, according to Yarnold. Future research is focused on the molecular mechanisms that determine fraction size sensitivity, which may lead to individualization of fraction size.

“It is likely that some breast cancers are more or less sensitive than others,” Yarnold said. “We are also testing a one-week schedule of whole breast radiotherapy against our new three-week standard in the U.K. FAST-Forward Trial.”

The START trials were funded by Cancer Research U.K., the U.K. Medical Research Council and the U.K. Department of Health.

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Sentinel Lymph Node Surgery After Chemotherapy Demonstrated Accuracy in Nodal Staging for Certain Patients With Breast Cancer

registration@aacr.org () — Wed, 05 Dec 2012 12:00:00 GMT

Presurgery chemotherapy eradicated lymph node disease in 40 percent of cases.
Sentinel lymph node surgery after chemotherapy correctly identified nodal status in 91 percent of patients.
False negative rate of SNL surgery was 12.6 percent.
Once chemotherapy is completed, this surgery may be reasonable for nodal staging in node-positive cases.

SAN ANTONIO — Sentinel lymph node surgery correctly identified nodal status after treatment with neoadjuvant chemotherapy in 84 percent of patients with node-positive breast cancer and could therefore provide a less invasive option than axillary lymph node dissection for nodal staging in this population, according to data from the American College of Surgeons Oncology Group (ACOSOG) Z1071 study.

These results were presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

Most women with breast cancer that has spread to their lymph nodes undergo an axillary lymph node dissection (ALND). However, treatment with chemotherapy before surgery, or neoadjuvant chemotherapy, can eradicate disease in the lymph nodes of some patients, converting them to node-negative status.

Sentinel lymph node (SLN) surgery is routinely used for patients initially diagnosed with node-negative disease. Judy C. Boughey, M.D., associate professor of surgery at the Mayo Clinic in Rochester, Minn., and her colleagues evaluated whether this technique could be safe for patients with node-positive breast cancer who undergo neoadjuvant chemotherapy.

In the case of node-positive breast cancer, “the question arises as to whether removal of the lymph nodes with an ALND is needed, or whether less invasive surgery, with a sampling of the nodes by SLN surgery alone, would reliably identify which patients still have disease in the lymph nodes and which patients have negative lymph nodes,” said Boughey.

The researchers conducted a multicenter study of 756 women with node-positive breast cancer who received neoadjuvant chemotherapy and underwent surgery. The study was performed through the American College of Surgeons Oncology Group (ACOSOG) and supported by the NCI.

Of these patients, 637 underwent both SLN surgery with identification and removal of the sentinel nodes under the arm and ALND to remove most of the lymph nodes in the axilla. SLN surgery correctly identified nodal status in 91 percent of patients, including 255 patients now with node-negative breast cancer and 326 patients with continuing node-positive disease.

Boughey and her colleagues also found that 40 percent of the patients for which an SLN could be identified showed a complete pathological response in the lymph nodes, or eradication of active disease in the lymph nodes.

“If SLN surgery is accurate for evaluating the lymph nodes after neoadjuvant chemotherapy, it potentially could allow patients to avoid ALND and undergo SLN for axillary staging and only require an ALND if the SLN is positive,” Boughey said.

Boughey noted a false-negative rate of 12.6 percent.

“This rate is lower with use of dual tracer (blue dye and radiolabelled colloid) to identify the SLN, and the false-negative rate is lower the more SLNs are removed. Therefore, technical factors are important to minimize incorrect nodal staging,” she said.

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Black Women Less Likely to Receive Improved Surgical Procedure for Breast Cancer

registration@aacr.org () — Wed, 05 Dec 2012 12:00:00 GMT

Data from 2002 to 2007 show a consistent disparity.
Black women were 12 percent less likely to receive newer surgical practice.
More efforts are needed to widely implement improved techniques.

SAN ANTONIO — Black women with breast cancer were 12 percent less likely than white women with the disease to receive a more minimally invasive procedure — sentinel lymph node biopsy — for staging of breast cancer, according to data tracking the treatment of patients through 2007.

“These findings are an example of the need for continued improvements in disseminating national practice guidelines for breast cancer to surgeons and other breast cancer providers in all of our communities,” said Dalliah Mashon Black, M.D., assistant professor of surgery in the department of surgical oncology at The University of Texas MD Anderson Cancer Center in Houston. Black presented the data at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

Axillary sentinel lymph node (SLN) biopsy became a recommended alternative to the more invasive procedure of axillary lymph node dissection (ALND) for staging clinically node-negative breast cancer in the mid-2000s. Although effective, ALND is associated with increased short-term and long-term complications, according to Black.

Using data from the Surveillance, Epidemiology and End Results (SEER)-Medicare database, Black and colleagues evaluated whether there was a difference in the utilization of SLN biopsy in black patients compared to white patients and whether this difference impacted the risk for lymphedema, which is a complication characterized by arm swelling that may occur after axillary surgery.

Data were from 31,274 women aged 66 or older, including 1,767 black women, 27,856 white women and 1,651 women of other or unknown race.

Sixty-two percent of black women underwent SLN biopsy compared with 74 percent of white women. The use of SLN biopsy increased each year for all patients, but disparities persisted through 2007.

“From 2002, when surgeons were still incorporating SLN biopsy into practice, until 2007, black women were less likely to have undergone an SLN biopsy than were white women,” Black said. “The fact that this disparity continued over time shows that new and improved surgical therapies may not be effectively implemented in some patient populations.”

Black women remained significantly less likely to receive SLN biopsy compared with white women despite adjustment for tumor size, patient sociodemographics and type of breast surgery. Furthermore, ALND was associated with twice the risk for lymphedema in black patients compared with patients treated with SLN biopsy.

Black and colleagues hope to update this study with data from the 2010 SEER-Medicare database to evaluate whether improvements have been made since 2007.

Black stressed that these data highlight the need for improving national implementation of changes in practice standards and for understanding how physician cancer teams incorporate recommendations in different patient populations.

“When we think of disparities, it doesn’t only mean that patients might be undertreated, but they could be overtreated with unnecessary and more radical procedures, leading to a higher risk for complications, as shown in this study,” she said.

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Extending Duration of Adjuvant Tamoxifen Treatment to 10 Years Reduced Risk for Late Breast Cancer Recurrence, Improved Survival

registration@aacr.org () — Wed, 05 Dec 2012 12:00:00 GMT

Greatest additional benefit was seen in the second decade after diagnosis.
Findings are directly relevant to women taking tamoxifen.
Women on other ER-positive breast cancer endocrine treatments may benefit.

SAN ANTONIO — Ten years of adjuvant treatment with tamoxifen provided women with estrogen receptor-positive breast cancer greater protection against late recurrence and death from breast cancer compared with the current standard of five years of tamoxifen, according to the international ATLAS (Adjuvant Tamoxifen — Longer Against Shorter) study.

“Five years of adjuvant tamoxifen is already an excellent treatment that substantially reduces the 15-year risk for recurrence and death from estrogen receptor (ER)-positive breast cancer, but ATLAS now shows that 10 years of tamoxifen is even more effective,” said Christina Davies, M.D., a coordinator in the Clinical Trial Service Unit at the University of Oxford in the United Kingdom.

She presented the results at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8. The results were simultaneously published in the Lancet.

“The main additional benefit from continuing tamoxifen treatment is to reduce breast cancer mortality during the second decade after diagnosis,” Davies said. “We already knew that five years of tamoxifen reduces breast cancer mortality in this late period by almost a third in comparison with no tamoxifen. We now know that 10 years of tamoxifen is even better, approximately halving breast cancer mortality during the second decade after diagnosis.”

Researchers enrolled 6,846 women with ER-positive breast cancer between 1996 and 2005. Half had node-positive disease. All the women had been using tamoxifen for five years, and the researchers randomly assigned them to continue treatment for another five years or to stop immediately.

After about eight years of follow-up, the researchers observed 1,328 breast cancer recurrences and 728 deaths after recurrence. The treatment allocation had little effect on either recurrence rates or death rates during the period five to nine years after diagnosis. However, during the second decade following diagnosis, the women who continued tamoxifen treatment had a 25 percent lower recurrence rate and a 29 percent lower breast cancer mortality rate compared with women who stopped after five years.

Risk for death from breast cancer five to 14 years after diagnosis was 12.2 percent among those who continued use versus 15 percent among those who stopped — an absolute gain of 2.8 percent. The researchers observed the greatest benefit during 10 to 14 years after diagnosis.

Davies noted that continuing tamoxifen use can increase side effects, with endometrial cancer being the most life-threatening. Because endometrial cancer is generally curable, the cumulative risk for death between five and 14 years after diagnosis was 0.4 percent versus 0.2 percent. Because this risk is heavily outweighed by the reduction in breast cancer deaths, overall mortality was significantly reduced by longer treatment. In premenopausal women, for whom tamoxifen is often the endocrine treatment of choice, there was no apparent excess of endometrial cancer.

“Many women with ER-positive breast cancer take tamoxifen, or some other adjuvant endocrine treatment, but the current recommendation is to stop after five years,” said Davies. “ATLAS showed that protection against breast cancer recurrence and death is greater with 10 years than with five years of tamoxifen use. Women and their doctors should be aware of this evidence when deciding how long to continue tamoxifen, or any other endocrine treatment.”

The study was funded by Cancer Research U.K., the U.K. Medical Research Council, AstraZeneca, the United States Army and the European Union.

# # #

Higher Doses of Fulvestrant Prolonged Survival in Patients With Advanced Breast Cancer

registration@aacr.org () — Wed, 05 Dec 2012 12:00:00 GMT

Improved survival seen with 500-mg dose versus 250-mg dose in patients with ER-positive metastatic disease.
Toxicity profiles were similar between dosage groups.

SAN ANTONIO — Increasing the dose of fulvestrant from 250 mg to 500 mg improved median overall survival in women with locally advanced or metastatic estrogen receptor-positive breast cancer, according to updated data from the CONFIRM trial presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

The Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) trial is a randomized, double-blind, parallel-group, multicenter, phase III trial of postmenopausal women with estrogen receptor (ER)-positive advanced breast cancer that recurred or progressed following endocrine therapy.

“Of note, the improvement in survival with the higher dose of fulvestrant was achieved without increasing treatment toxicity. Indeed, the dose of 500 mg had the same toxicity profile as the 250-mg dose,” said Angelo Di Leo, M.D., Ph.D., head of the department of medical oncology at the Hospital of Prato, Istituto Toscano Tumori in Prato, Italy.

Between February 2005 and August 2007, researchers randomly assigned 736 women from 128 centers in 17 countries to 250 mg or 500 mg of fulvestrant and followed them until 75 percent of the patients died. At the time of analysis, 554 patients had died, 63 were lost to follow-up and 16 withdrew consent.

Among the entire study population, the 500-mg dose was associated with a clinically relevant 4.1-month difference in median overall survival compared with the lower dose: 26.4 months in the 500-mg group and 22.3 months in the 250-mg group. Researchers also saw a 19 percent reduction in risk for death in the 500-mg group compared with the 250-mg group. Serious adverse events occurred in 8.9 percent of patients who had received the 500-mg dose and in 6.7 percent of patients in the 250-mg group.

“For those postmenopausal women with recurrent or progressing ER-positive locally advanced or metastatic breast cancer for whom fulvestrant is the appropriate treatment choice, the standard of care is a 250-mg dose,” said Di Leo. “Our results indicate that this should be modified to a 500-mg dose.”

According to Di Leo, the next research step will be to study 500 mg of fulvestrant in combination with biological agents, such as PI3K inhibitors or anti-HER2 agents that can reverse resistance to endocrine therapy.

“This approach could further increase the activity of fulvestrant given at the 500-mg dose,” he said.

# # #

Combination of Investigational Agent and Letrozole Demonstrated Clinical Benefit in Advanced ER-positive Breast Cancer

registration@aacr.org () — Wed, 05 Dec 2012 12:00:00 GMT

Combination improved progression-free survival and was well tolerated.
Investigational agent is an oral selective inhibitor of cyclin-dependent kinase 4/6.

SAN ANTONIO — The combination of the investigational agent PD 0332991 and letrozole significantly improved median progression-free survival in patients with advanced estrogen receptor-positive breast cancer, according to phase II results presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

“We are very encouraged by this improvement in progression-free survival,” said Richard S. Finn, M.D., associate professor of medicine at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

PD 0332991, which is being developed by Pfizer Inc., is a novel oral selective inhibitor of cyclin-dependent kinase (CDK) 4/6, which prevents cellular DNA synthesis by blocking cell cycle progression, Finn said. Previously published preclinical data have suggested that CDK 4/6 inhibition may play a role in the treatment of some breast cancers.

In the first part of this two-part, phase II study, Finn and colleagues randomly assigned 66 postmenopausal women with metastatic estrogen receptor (ER)-positive breast cancer to either the combination of PD 0332991 and letrozole or to letrozole alone. The second part of the study involved 99 patients with ER-positive cancers determined by screening to have certain genomic alterations, specifically cyclin D1 amplification and/or p16 loss, according to Finn.

Results showed that progression-free survival was 26.1 months for those in the combination arm versus 7.5 months for patients treated with letrozole alone. There was also a 45 percent response rate with the combination treatment versus 31 percent with letrozole alone in patients with measurable disease. The clinical benefit rate was 70 percent with the combination treatment and 44 percent with letrozole alone.

The combination of PD 0332991 and letrozole was also well tolerated. The most common adverse events were neutropenia, leukopenia, anemia and fatigue. “Importantly, this was uncomplicated neutropenia,” Finn said. “There was no evidence of febrile neutropenia.”

Further, after retrospectively analyzing the biomarkers for cyclin D1 amplification or p16 loss, the researchers found that “ER positivity was the only biomarker we really needed to select patients who were most likely to benefit from PD 0332991,” he said.

“If these results are verified in a large, phase III study this could establish PD 0332991 as an important new treatment option for advanced ER-positive breast cancer in a frontline setting.”

# # #

AACR Launches New Journal: Cancer Immunology Research

registration@aacr.org () — Mon, 03 Dec 2012 12:00:00 GMT

Call for Submissions Pertaining to Immunology in Cancer Research Now Open

PHILADELPHIA — The American Association for Cancer Research has announced the launch of its newest peer-reviewed journal, Cancer Immunology Research, which will publish groundbreaking original articles on major advances in cancer immunology along with exciting feature articles.

Cancer Immunology Research is now receiving manuscripts for consideration for publication through the journal’s online site. It will launch online at the 2013 AACR Annual Meeting and offer continuous online publication, followed by a monthly in print issue beginning in June 2013.

The journal will publish research articles reporting major advances in all areas of cancer immunology, including basic investigations in host–tumor interactions, developmental therapeutics in model systems, early translational studies in patients and clinical trials.

In addition to research and review articles, the journal will include special features such as “Masters of Immunology,” which will be primers by leading immunologists, and “Cancer Immunology at the Crossroads,” which will be perspectives that highlight the relationship between immunology and other areas of cancer research and allied disciplines.

“The AACR has long supported the information exchange regarding cancer immunology in various ways including special conferences, meeting sessions and published articles,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “We are committed to extending these efforts and to addressing the needs of cancer researchers through the launch of this new journal. Cancer Immunology Research is an outstanding addition to the AACR’s publications program. We are confident it will capture the most significant work in the field and inspire new thinking that will accelerate advancements in cancer biology and treatment.”

Glenn Dranoff, M.D., professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School in Boston, Mass., is the founding editor-in-chief of Cancer Immunology Research. He is also the Leader of the Dana-Farber/Harvard Cancer Center Program in Cancer Immunology. Dranoff has devoted much of his career and research efforts to understanding the mechanisms underlying the stimulation of tumor immunity and to applying these discoveries to the development of cancer vaccines.

“Cancer Immunology Research will play a leading role in educating the greater cancer research community regarding the principles and opportunities in cancer immunology,” said Dranoff. “Recent clinical successes have validated the longstanding idea that therapeutic manipulation of the immune system may achieve meaningful antitumor effects.”

“My vision is that by disseminating new knowledge of cancer immunology, this journal will catalyze cross-disciplinary work that yields a deeper understanding of the host–tumor relationship, more potent cancer treatments and improved clinical outcomes,” he added.

Specific topics of interest for publication include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies and clinical investigations.

Cancer Immunology Research is the eighth peer-reviewed scientific journal to be added to the AACR’s prestigious publications portfolio. The AACR also publishes a magazine for cancer survivors, patients and their caregivers.

For instructions on how to submit a manuscript for publication in Cancer Immunology Research, please visit http://www.aacrjournals.org/site/InstrAuthors/ifora.xhtml.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Two Leading Researchers to Be Honored at the 35th Annual CTRC-AACR San Antonio Breast Cancer Symposium

registration@aacr.org () — Wed, 28 Nov 2012 12:00:00 GMT

SAN ANTONIO — The 2012 CTRC-AACR San Antonio Breast Cancer Symposium will honor two leading breast cancer researchers during its 35th annual symposium, which will be held here Dec. 4-8 at the Henry B. Gonzales Convention Center.

Kornelia Polyak, M.D., Ph.D., will receive the 2012 AACR Outstanding Investigator Award for Breast Cancer Research, and Mina J. Bissell, Ph.D., will present the 2012 AACR Distinguished Lectureship in Breast Cancer Research.

Hosted by the Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio, the AACR and Baylor College of Medicine, the symposium is a four-day program that presents a balance of clinical, translational and basic research focused on breast cancer. It provides a forum for interaction, communication and education for a broad spectrum of researchers, health care professionals and those with a special interest in breast cancer.

2012 AACR Outstanding Investigator Award for Breast Cancer Research, funded by Susan G. Komen for the Cure

Polyak will deliver her award lecture, “Breast Tumor Evolution: Drivers and Clinical Relevance,” on Thursday, Dec. 6 at 11:30 a.m. CT in Exhibit Hall D of the Henry B. Gonzalez Convention Center.

Polyak is a professor of medicine in the department of medical oncology at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Mass. Her laboratory investigates the molecular basis of breast tumor evolution, with special emphasis on the role of the microenvironment and intratumor diversity in these processes. Her work focuses on identifying molecular alterations between normal and cancerous breast tissue using various technologies, determining their consequences and utilizing them to improve the clinical management of patients with breast cancer.

Funded by Susan G. Komen for the Cure, this award recognizes an investigator younger than 50 whose novel and significant work has had or may have a far-reaching impact on the etiology, detection, diagnosis, treatment or prevention of breast cancer.

2012 AACR Distinguished Lectureship in Breast Cancer Research, supported by Bristol-Myers Squibb

Bissell will deliver her award lecture, titled “Genes and the Microenvironment: The Two Faces of Breast Cancer,” on Friday, Dec. 7 at 11:30 a.m. CT in Exhibit Hall D of the Henry B. Gonzales Convention Center.

Bissell is a distinguished scientist at Lawrence Berkeley National Laboratory in Berkeley, Calif. Her innovative breast cancer research has had a profound influence on the understanding of cancer biology, in particular how three-dimensional organ architecture is responsible for normal behavior and how the loss of this crucial information influences the genesis of tumors. Her work demonstrated the pivotal role of reciprocal signaling between the nucleus and the extracellular matrix that surrounds tissues. She argued that it is the imbalance of this dynamic exchange of information that causes cancer. The research generated by Bissell and her team indicates that it is not only the genetic mutations that drive cancer, but also disruption of microenvironmental control.

Supported by Bristol-Myers Squibb, this lectureship was established in 2008 and is given annually to an individual who has undertaken outstanding scientific research that has inspired or has the potential to inspire new perspectives on the etiology, diagnosis, treatment or prevention of breast cancer.

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The mission of the CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR’s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit www.sabcs.org.

Media Contact:
Tara Yates
(215) 446-7110
Tara.Yates@aacr.org
In San Antonio, Dec. 4-8:
(210) 582-7035

AACR and Millennium Partner to Offer Two New Grant Opportunities for Lymphoma Research and Prostate Cancer Research

registration@aacr.org () — Tue, 27 Nov 2012 12:00:00 GMT

The call for applications is open now through Jan. 7, 2013.

PHILADELPHIA — The American Association for Cancer Research and Millennium: The Takeda Oncology Company are pleased to announce a new partnership and call for applications for two grant opportunities to support lymphoma and prostate cancer research.

The 2013 AACR-Millennium Fellowship in Lymphoma Research and the 2013 AACR-Millennium Fellowship in Prostate Cancer Research will each provide young cancer researchers with $55,000 over one year.

“The AACR is very proud to collaborate with Millennium and provide additional fellowship opportunities to promising young investigators who have strong potential to become productive and successful independent cancer researchers,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “As we add these new fellowships to the AACR’s growing grants portfolio, we know they will aid in filling the gaps in the areas of lymphoma and prostate cancer, where more research is greatly needed.”

“At Millennium we’re very excited to partner with the AACR to increase the educational opportunities for young researchers in the area of oncology,” said Karen Ferrante, M.D., chief medical officer at Millennium. “In our efforts to make a dramatic impact on cancer therapeutics, we are dedicated to a strong partnership with the AACR and the oncology community. As leaders in the biopharmaceutical industry we’re very proud to be helping develop the next group of young scientists who will share in that effort.”

Qualified applicants must have a doctoral degree, be in the first five years of their postdoctoral or clinical research fellowship at the start of the grant term and work under the auspices of a mentor at an academic, medical or research institution within the United States. AACR members and nonmembers are eligible to apply; however, nonmembers must submit an application for AACR associate membership. Proposed mentored cancer research projects must have direct applicability and relevance to either lymphoma research or prostate cancer research.

Young investigators who are interested in applying can click here for additional details. Applications must be submitted to the AACR by noon ET on Monday, Jan. 7, 2013, using the proposalCENTRAL website. A hard copy with original signatures must also be mailed to the AACR at 615 Chestnut Street, 17th Floor, Philadelphia, PA 19106, Attn.: Hanna Hopfinger, postmarked no later than Jan. 9. Additional inquires may be directed to grants@aacr.org.

Selected recipients will be announced during a grants ceremony at the AACR Annual Meeting held April 6-10, 2013, in Washington, D.C., and they will also receive a commemorative plaque. The start date for the AACR-Millennium Fellowship in Lymphoma Research and the AACR-Millennium Fellowship in Prostate Cancer Research is July 1, 2013.

The AACR’s research fellowships program was first established in 1996, and to date has distributed more than $6 million in cancer research funding.

# # #

Media Contacts:
Tara Yates
American Association for Cancer Research
(215) 446-7110
Tara.Yates@aacr.org

David Albaugh
Millennium: The Takeda Oncology Company
(617) 444-4456
David.Albaugh@MPI.com

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org. Follow the AACR on Twitter: @aacr #aacr Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About Millennium
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. (“Takeda”, TSE: 4502) in May, 2008. The Company’s research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, www.millennium.com.

Novel Mechanism Through Which Normal Stromal Cells Become Cancer-promoting Stromal Cells Identified

registration@aacr.org () — Wed, 21 Nov 2012 12:00:00 GMT

Change in three microRNAs’ expression converted normal fibroblasts to cancer-associated fibroblasts.
Restoring the pattern of microRNA expression reduced cancer-promoting qualities.
Cytokines regulated by these specific microRNAs represent potential new targets for ovarian cancer treatment.

PHILADELPHIA — New understanding of molecular changes that convert harmless cells surrounding ovarian cancer cells into cells that promote tumor growth and metastasis provides potential new therapeutic targets for this deadly disease, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

“New approaches for treating patients with ovarian cancer are desperately needed,” said Ernst Lengyel, M.D., Ph.D., professor in the department of obstetrics and gynecology at the University of Chicago. “There have been no new approaches introduced into the clinic for quite some time, and we have seen no major improvements in patient survival over the years.”

According to Lengyel, greater understanding of the biology of ovarian cancer should provide new therapeutic targets. He and his colleagues set out to learn how normal stromal cells are transformed into cancer-associated fibroblasts, which are found in the tissue immediately surrounding the ovarian cancer cells. Intimate cross talk between cancer-associated fibroblasts and cancer cells boosts tumor growth and metastasis.

“The strength of our study lies in the fact that we used cells from patients, rather than cell lines,” said Lengyel. “This means that our model system reflects as closely as possible the clinical situation in patients.”

Initial analysis indicated that cancer-associated fibroblasts from patients with ovarian cancer had altered patterns of expression of small molecules called microRNAs compared with normal and tumor-adjacent fibroblasts.

MicroRNAs are important regulators of gene expression because they help direct that cell’s function. Thus, modified patterns of microRNA expression change cell function.

Lengyel and colleagues further studied the microRNA most upregulated in cancer-associated fibroblasts and the two microRNAs most significantly downregulated. When they changed the pattern of expression of these three microRNAs in normal fibroblasts to mimic the pattern they had seen in cancer-associated fibroblasts, they found that the normal fibroblasts were converted into cells with in-vitro characteristics of cancer-associated fibroblasts. Moreover, the cells reprogrammed to become cancer-associated fibroblasts by altering microRNA expression enhanced the growth of tumor cells in a mouse model of ovarian cancer.

Conversely, restoring the pattern of expression of the three microRNAs to normal in cancer-associated fibroblasts reduced their cancer-promoting characteristics.

“Therapeutic approaches targeting microRNAs in cancer cells are under development,” said Lengyel. “Our work suggests that it might be possible to modify microRNA expression in cancer-associated fibroblasts for therapeutic benefit.”

Lengyel added that treatments targeting microRNAs in cancer-associated fibroblasts may be particularly effective because these cells are genetically stable, unlike cancer cells, therefore, the risk that cancers will become unresponsive to these treatments is less than for treatments targeting cancer cells.

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Karen E. Knudsen, Ph.D., Named New Editor-in-chief of AACR Journal Molecular Cancer Research

registration@aacr.org () — Thu, 15 Nov 2012 12:00:00 GMT

PHILADELPHIA — The American Association for Cancer Research is pleased to announce Karen E. Knudsen, Ph.D., professor and Hilary Koprowski chair in the departments of cancer biology, urology and radiation oncology at Thomas Jefferson University in Philadelphia, and deputy director for basic science of the NCI-designated Kimmel Cancer Center as the new editor-in-chief of Molecular Cancer Research, one of its seven major peer-reviewed journals.

“I am honored and excited for the opportunity to lead Molecular Cancer Research,” said Knudsen, who will serve as the journal’s editor-in-chief for five years. “I hope to establish the journal as the seat of outstanding basic research related to cancer.”

Knudsen will officially begin her term in January 2013.

Molecular Cancer Research is an online and print journal that publishes original, novel and well-designed studies on the molecular and cellular aspects of cancer biology. Papers selected for publication represent new information in basic research that has implications for cancer therapeutics in angiogenesis, metastasis or genomics. The first issue of the journal was published in November 2002.

“Dr. Knudsen brings a wealth of expertise to the position of editor-in-chief of Molecular Cancer Research,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “We are confident that her experience with the peer review process, coupled with her extensive knowledge of basic cancer research, will build on the journal’s success and impact in the field.”

Knudsen’s scientific accomplishments include the authorship of more than 80 peer-reviewed publications in cancer and biomedical science journals. In addition, she has authored numerous book chapters focusing on transcription and cell cycle regulation in hormone-dependent cancers. Knudsen’s research interest is predominantly prostate cancer and the molecular mechanisms that underlie tumor progression.

Throughout her career, Knudsen has been involved in both national and international scientific committees, and has held numerous leadership roles in scientific publishing, including Cancer Research. She recently received the Excellence in Mentoring Award from Thomas Jefferson University, the Richard E. Weitzman Laureate Award from the Endocrine Society and the Ron Ross Award from the Pacific Rim Breast and Prostate Cancer Foundation.

Knudsen received her doctorate from the University of California, San Diego in 1996. She trained as a postdoctoral fellow at the Ludwig Institute for Cancer Research with Webster K. Cavenee, Ph.D.

Knudsen served as assistant professor in the department of cell and cancer biology at the University of Cincinnati College of Medicine for five years and was promoted to associate professor with tenure in 2005. Two years later she joined Thomas Jefferson University as an associate professor in the departments of cancer biology and urology. In 2010, Knudsen was promoted to professor, and in addition to her duties as the deputy director of the Kimmel Cancer Center, she currently serves as the program leader for the Kimmel Cancer Center Program in Biology of Prostate Cancer.

Knudsen succeeds Michael B. Kastan, M.D., Ph.D., executive director of the Duke Cancer Institute, as editor-in-chief of the journal.

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy Moore@aacr.org

Potential New Technique for Anticancer Radiotherapy Could Provide Alternative to Brachytherapy

registration@aacr.org () — Thu, 15 Nov 2012 12:00:00 GMT

New approach could be alternative to surgical implantation of radioactive “seeds.”
Injected radioactive substance was retained in tumors in mice.
Tumor growth was delayed in all treated animals.

PHILADELPHIA — A promising new approach to treating solid tumors with radiation was highly efficacious and minimally toxic to healthy tissue in a mouse model of cancer, according to data published in Cancer Research, a journal of the American Association for Cancer Research.

Some patients with solid tumors, including prostate cancer, are treated using a clinical technique called brachytherapy. Brachytherapy involves the surgical implantation of radioactive “seeds” within a patient’s tumor to expose the tumor cells to high levels of radiation while minimizing the negative side effects of radiation on the rest of the body.

“The use of brachytherapy is limited by several factors,” said Wenge Liu, M.D., Ph.D., associate research professor of biomedical engineering at Duke University in Durham, N.C. “The most prominent factor is the need for surgical implantation and removal of the seeds. We set out to develop an alternative approach to brachytherapy that would eliminate the need for surgery.”

Liu and his colleagues generated an injectable substance, called a polymer, attached to a source of radioactivity that spontaneously assembled into a radioactive seed after being injected into a tumor.

In all mice transplanted with either a human head and neck cancer cell line or a human prostate cancer cell line, injection of the radioactive polymers into the growing tumors substantially delayed tumor growth. In more than 67 percent of the animals, the tumors were eradicated by a single injection. Further analysis indicated no signs that cells outside the tumor had been exposed to significant amounts of radiation in any of the animals injected with the radioactive polymers.

“We believe that this approach provides a useful alternative to existing brachytherapy, which requires a complicated surgical procedure to implant the radioactive seeds,” Liu said. “Moreover, these injectable seeds degrade after the radiation is exhausted, so they do not need to be surgically removed.”

# # #

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Combination of PI3-kinase and PARP Inhibitors May Offer New Treatment Option for Triple-negative Breast Cancers

registration@aacr.org () — Mon, 12 Nov 2012 12:00:00 GMT

PI3-kinase inhibitors sensitized tumors to PARP inhibitors.
Combination significantly prolonged progression-free survival in mouse model.

PHILADELPHIA — The simultaneous inhibition of two separate and seemingly unrelated pathways could potentially provide an effective treatment for women with triple-negative breast cancer, according to results of two studies published in the November issue of Cancer Discovery, a journal of the American Association for Cancer Research.

Triple-negative breast cancers do not express three common targets of breast cancer treatments: the estrogen receptor, progesterone receptor and HER2/neu. As a result, women with triple-negative breast cancer have few treatment options. In early-phase clinical studies, those women with triple-negative breast cancer with BRCA1 gene mutations had some clinical benefit from treatments with poly-ADP-ribose-polymerase (PARP) inhibitors. However, the activity of the PARP inhibitors is short-lived.

“We are in desperate need of new therapies for triple-negative breast cancer, which is a type of breast cancer that is very aggressive and occurs mostly in young females,” said José Baselga, M.D., Ph.D., chief of the division of hematology and oncology at Massachusetts General Hospital Cancer Center in Boston.

In their study, Baselga; Yasir Ibrahim, Ph.D., a postdoctoral fellow at Vall D’Hebron Institute of Oncology in Barcelona, Spain; and Maurizio Scaltriti, Ph.D., faculty assistant and lab coordinator at Massachusetts General Hospital Cancer Center, hypothesized that inhibiting PI3-kinase, a key component of a signaling pathway frequently activated inappropriately in triple-negative breast cancer, would replicate the conditions present in BRCA-mutated breast cancers, thereby increasing sensitivity to PARP inhibitors.

They found that if PI3-kinase function was blocked in a BRCA-proficient triple-negative breast cancer cell line, DNA damage would occur due to BRCA protein downregulation, and that this resulted in activation of PARP to repair the damage.

“In a way, with PI3-kinase inhibitors, we are converting BRCA-proficient triple-negative breast cancer into BRCA-deficient breast cancer and, therefore, these cells become sensitive to PARP inhibition,” Baselga said.

In the second study, Lewis C. Cantley, Ph.D.; Gerburg Wulf, M.D., Ph.D.; and colleagues used an endogenous mouse model of BRCA1-deficient breast cancer. They observed that mice with a BRCA1 mutation also had molecular indicators of strong activation of the PI3-kinase pathway, suggesting that the tumors might be vulnerable to PI3-kinase inhibitors.

When the mice were treated with a PI3-kinase inhibitor, tumor doubling was delayed from five to 26 days. Given that BRCA-mutated tumors are also known to respond to PARP inhibitors, the researchers combined the two medications and found that this delayed tumor doubling to more than 70 days.

“We saw in vivo synergy that led to dramatic prolongation of progression-free survival in these mice of more than two to three months, which in the life of a mouse is very long,” said Wulf, staff physician in the division of hematology and oncology at Beth Israel Deaconess Medical Center. “This is an unusual observation that makes us hopeful that it is worthwhile to explore in an early-phase clinical trial.”

Both studies received funding from Stand Up To Cancer Dream Team Translational Research Grants.

Cantley, who conducted the research while director of the cancer center at Beth Israel Deaconess Medical Center in Boston, and his colleagues have worked with Novartis and AstraZeneca, the two companies that manufacture the PI3-kinase inhibitor (BKM120) and the PARP inhibitor (Olaparib) to initiate a clinical trial combining the two drugs in humans.

Cantley said it is extremely unusual for two unapproved drugs to be combined in a cancer clinical trial, especially when the two drugs are produced by separate companies. Yet the preclinical results were sufficiently compelling to accelerate the initiation of this trial. The trial, led by Ursula Matulonis, M.D., director of medical gynecologic oncology at the Dana-Farber Cancer Institute in Boston, is now open and starting to enroll patients with triple-negative breast or ovarian cancer.

“This is truly an amazing story where essentially the same week that the paper is coming out showing an observation, the clinical trial is starting,” Cantley said. “This type of bench-to-bedside process typically takes five to 10 years but was dramatically accelerated by the collaborative efforts of the Stand Up To Cancer-funded PI3-Kinase Dream Team.”

# # #

Follow the AACR on Twitter: @aacr #aacr
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

New Mechanism of Action for PARP Inhibitors Discovered

registration@aacr.org () — Fri, 09 Nov 2012 12:00:00 GMT

PARP inhibitors are promising treatments for BRCA-mutant breast and ovarian cancers.
Researchers have identified a new way in which these drugs work.
New genetic mutations rendering cells susceptible to PARP inhibitors are also identified.
Patients with tumors bearing these mutations might benefit from PARP inhibitors.

PHILADELPHIA — New understanding of how drugs called PARP inhibitors, which have already shown promise for the treatment of women with familial breast and ovarian cancers linked to BRCA mutations, exert their anticancer effects has led to the identification of ways in which the patient population that might benefit from PARP inhibitors could be expanded.

Yves Pommier, M.D., Ph.D., chief of the Laboratory of Molecular Pharmacology at the National Cancer Institute’s Center for Cancer Research in Bethesda, Md., and colleagues reported these data in Cancer Research, a journal of the American Association for Cancer Research.

“In recent years, drugs classified as poly (ADP-ribose) polymerase (PARP) inhibitors have been shown to be promising anticancer agents for breast and ovarian cancers deficient in either BRCA1 or BRCA2,” said Pommier. “Prior to our study, PARP inhibitors were thought to work primarily by blocking the DNA repair function of members of the PARP family of proteins, leading ultimately to cancer cell death.”

In their initial studies, Pommier and his colleagues found that the PARP inhibitor olaparib was more toxic to cultured cells than genetic elimination of PARP1.

According to Pommier, these results indicated that olaparib must have additional modes of action, and their detailed cellular analyses identified a critical one: olaparib was trapping PARP proteins, specifically PARP1 and PARP2, at sites of DNA damage, and the trapped PARP protein-DNA complexes were highly toxic to cells.

When the trapping ability of olaparib was compared with that of two other PARP inhibitors under clinical development, it was found that the trapping potency of the three drugs differed markedly: niraparib was more potent than olaparib, which was in turn substantially more potent than veliparib. In contrast, olaparib was the most potent inhibitor of DNA repair function, followed by veliparib and then niraparib.

“Critical to this study, is the demonstration that PARP inhibitors are not equivalent with respect to their potency to trap PARP proteins,” said Pommier. “Our findings indicate that PARP inhibitors should be categorized according to their potency to trap PARP, in addition to their ability to inhibit DNA repair. This is important because it might explain differences in the results of clinical trials using distinct PARP inhibitors.”

In further experiments, the researchers identified several genetic mutations in post-replication repair and Fanconi anemia pathways that, like BRCA1 and BRCA2 mutations, sensitized cultured cells to the toxic effects of trapped PARP protein-DNA complexes.

“These data suggest that patients with cancers deficient in these PARP inhibitor-sensitizing genes might benefit from treatment with PARP inhibitors,” said Pommier. “It is clear, however, that this hypothesis will require rigorous testing before being broadly translated to the clinic.”

# # #

Follow the AACR on Twitter: @aacr #aacr
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Inflammation Marker Linked to Increased Risk for Death From Cancer in Korean Men

registration@aacr.org () — Wed, 07 Nov 2012 12:00:00 GMT

High levels of the inflammation marker hs-CRP associated with increased risk for cancer death.
No significant association was found in women.
The relationship was more common in lean participants.

PHILADELPHIA — Measuring blood levels of high-sensitive C-reactive protein, an important marker of inflammation, in apparently cancer-free men could potentially help identify those at increased risk for death from cancer, in particular lung cancer, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Inflammation has been linked to the initiation and progression of several types of cancer, as well as to the progression of atherosclerosis and cardiovascular disease,” said Minseon Park, M.D., Ph.D., M.P.H., assistant professor in the Department of Family Medicine at the Center for Health Promotion at Seoul National University Hospital in South Korea. “We wanted to determine whether there was a relationship between a well-established marker of inflammation, high-sensitive C-reactive protein (hs-CRP), and death from all causes, death from cancer or death from a site-specific cancer in Koreans.”

Park and colleagues retrospectively analyzed data from 33,556 individuals who had completed medical checkups, answered questions on cancer-related behavioral factors (like smoking status and exercise habits) and had been screened for blood hs-CRP at the health-screening center at Seoul National University Hospital between May 1995 and December 2006. During an average follow-up of 9.4 years, 1,054 deaths from all causes and 506 deaths from cancer were recorded.

When the researchers adjusted for several variables, including age, diabetes, smoking status and exercise habits, men with the highest level of hs-CRP in their blood (3 mg per liter or more) were 38 percent more likely to have died from any cause compared with men with the lowest hs-CRP level (1 mg per liter or less). They were also 61 percent more likely to have died from cancer.

For women, after adjusting for a number of variables, no statistically significant association was observed for hs-CRP level and death from any cause or death from cancer.

Through analysis of associations between hs-CRP levels and site-specific cancers, the researchers found that a significant relationship existed only for lung cancer. After adjusting for multiple variables, individuals with the highest hs-CRP level were more than twice as likely to die from lung cancer compared with those with the lowest hs-CRP level.

The association between hs-CRP levels and all-cause mortality and cancer mortality was stronger in lean individuals compared with those who were overweight.

“This was surprising,” said Park. “Because obesity is a major risk factor for chronic diseases like cancer, physicians and the mass media often recommend eating less and exercising more. While an important public health message, some people are too concerned with these recommendations and they eat fewer calories than their body actually needs. It is important that we eat enough to meet the metabolic demands of our body to make sure our organs function adequately for a healthy life.”

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Survivors of Certain Cancers Reported Poor Health-related Quality of Life Years After Diagnosis

registration@aacr.org () — Tue, 30 Oct 2012 12:00:00 GMT

Melanoma, breast and prostate cancer survivors reported quality of life similar to adults without cancer.
Cervical, blood, colorectal and short-survival cancer survivors reported worse health compared to adults without cancer.
The researchers estimated 3.3 million American cancer survivors have poor physical health.

PHILADELPHIA — Survivors of many common cancers enjoy a mental and physical health-related quality of life equal to that of adults who have not had cancer, but survivors of other cancers are in poorer health, according to results published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“We did not have a good sense of how cancer survivors across the United States were faring after their cancer diagnosis and immediate treatment,” said Kathryn E. Weaver, Ph.D., M.P.H., assistant professor at Wake Forest Baptist Medical Center in Winston-Salem, N.C. “We set out to address this issue by estimating the number and percent of cancer survivors in the United States with poor physical and mental health and compared them to adults who have never had a cancer diagnosis.”

Weaver and colleagues from the National Cancer Institute (NCI) and the Centers for Disease Control and Prevention (CDC) analyzed data from the 2010 National Health Interview Survey, a large survey conducted by the CDC to track trends in illness and disability in the United States. They identified a cohort of 1,822 cancer survivors and compared them with 24,804 adults with no history of cancer.

Patient-reported, health-related quality of life was assessed using the 10-item Patient-Reported Outcomes Measurement Information System Global Health Scale (PROMIS Global 10). This tool allows researchers to measure, from the patient perspective, health outcomes like physical functioning, depression, pain and fatigue.

After adjusting for gender, race/ethnicity, education and other medical conditions, it was found that the most recent form of cancer a patient was diagnosed with was significantly related to health-related quality of life. Survivors of breast cancer, prostate cancer and melanoma had a health-related quality of life equivalent to or better than adults with no cancer history.

In contrast, survivors of cervical, blood and colorectal cancers, as well as survivors of cancers with a five-year survival rate of less than 25 percent (such as cancers of the liver, lung and pancreas), had worse physical health-related quality of life. In addition, survivors of cervical cancer and cancers with a low five-year survival rate had worse mental health-related quality of life.

Twenty-five percent and 10 percent of cancer survivors in the analytic sample had lower than normal physical and mental health-related quality of life, respectively. Weaver and colleagues, therefore, estimated that 3.3 million cancer survivors in the United States have below-average physical health-related quality of life and almost 1.4 million have below-average mental health-related quality of life.

“It is very concerning that there are a substantial number of cancer survivors who experience poor mental or physical health years after cancer,” said Weaver. “Our results will serve as a baseline so that in five to 10 years, we can assess whether current approaches to improving the health and well-being of cancer survivors are having a positive effect.

“I also hope our data will draw attention to the ongoing needs of cancer survivors — particularly those with cervical, blood and less common cancers — and to the importance of monitoring these individuals, even long after their cancer diagnosis.”

The study was funded by the NCI.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Racial/Ethnic Disparities in Survival After Breast Cancer Remain Despite Similarities in Education, Neighborhood Socioeconomic Status

registration@aacr.org () — Mon, 29 Oct 2012 12:00:00 GMT

Breast cancer survival is known to differ across racial/ethnic groups.
More education, better neighborhood socioeconomic status improved survival rates.

SAN DIEGO — Disparities in survival after breast cancer persisted across racial/ethnic groups even after researchers adjusted for multiple demographics, such as patients’ education and the socioeconomic status of the neighborhood in which they lived, according to data presented at the Fifth AACR Conference on The Science of Cancer Health Disparities, held here Oct. 27-30, 2012.

“We learned that the effects of neighborhood socioeconomic status differed by racial/ethnic group. When simultaneously accounting for race/ethnicity and socioeconomic status, we found persistent differences in survival within and across racial/ethnic groups,” said Salma Shariff-Marco, Ph.D., M.P.H., a researcher at the Cancer Prevention Institute of California in Fremont.

Shariff-Marco and colleagues studied data from 4,405 patients with breast cancer who had participated in one of two population-based studies undertaken in the San Francisco Bay Area. Participants included 1,068 non-Latina whites, 1,670 Latinas, 993 African-Americans and 674 Asian-Americans.

All-cause survival was worse for African-Americans and better for Latinas and Asian-Americans compared with non-Latina whites after adjusting for age, study and tumor characteristics. When the researchers additionally adjusted for treatment and reproductive and lifestyle factors, they found that African-Americans had similar survival rates to non-Latina whites, but the survival rates of Latinas and Asian-Americans remained better.

Researchers also evaluated disparities in survival while considering racial/ethnic and socioeconomic status interactions. Compared with non-Latina whites with high education and high neighborhood socioeconomic status, worse survival was seen for African-Americans with low neighborhood socioeconomic status (regardless of education) and better survival was seen among Latinas with high neighborhood socioeconomic status (regardless of education) and Asian-Americans with high education and high neighborhood socioeconomic status.

The researchers noted that certain groups who were identified as having better or worse survival would benefit from further study to understand their risk profiles and target specific interventions.

“Understanding and addressing potential barriers to better survival are needed for groups with worse survival,” Shariff-Marco said. “One program that may be useful is patient navigation to ensure that these women are able to access and navigate the health care system. Sharing these findings with the broader public health community (e.g., health educators, community-based organizations and leaders) will also be helpful.”

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In San Diego, Oct. 27-30:
(619) 358-6870

Participation in Clinical Trials High Among Cancer Survivors Who Self-identify as Gay, Lesbian and Bisexual

registration@aacr.org () — Mon, 29 Oct 2012 12:00:00 GMT

Association is not explained by other demographic differences.
According to the researchers, their data should be interpreted cautiously.

SAN DIEGO — Cancer survivors who self-identified as being lesbian, gay or bisexual were more than twice as likely as heterosexual cancer survivors to have participated in cancer clinical trials, according to data from a small study presented at the Fifth AACR Conference on The Science of Cancer Health Disparities, held here Oct. 27-30, 2012.

“The data from which our findings were derived were incredibly limited. We have to interpret these data cautiously,” said Jennifer M. Jabson, M.P.H., Ph.D., a postdoctoral research fellow in the department of community health sciences at Boston University School of Public Health.

In 2011, the Institute of Medicine (IOM) issued a report titled “The Health of Lesbian, Gay, Bisexual and Transgender People: Building a Foundation for Better Understanding,” in which it identified this community as medically underserved. Jabson and colleagues studied the representation of the lesbian, gay and bisexual community in cancer clinical trials to add to existing knowledge about their experience with cancer and their participation in the clinical trial system.

The researchers used data from the Behavioral Risk Factor Surveillance System and an optional module that assesses cancer survivor participation in cancer clinical trials. They collected data from five states — Massachusetts, New Mexico, Wisconsin, Alaska and California — that used this module and an item asking self-identified lesbian, gay and bisexual status. The total population was 4,339 people.

“We thought there would be an under-representation of lesbian, gay and bisexual individuals in the data,” Jabson said. “We only found one prior paper that had been published in the last 10 years on the topic, and it found that individuals in this community were more often excluded in all clinical trials, not just those specific to cancer.”

However, the results of this study indicated that 12.5 percent of the cancer survivor population that self-identified as being lesbian, gay and bisexual participated in clinical trials compared with 6 percent of the heterosexual cancer survivor population. When adjusting the data to account for participants’ age, sex, education, race/ethnicity and survey location, cancer survivors from the lesbian, gay and bisexual community were more than twice as likely to report participation in a clinical trial.

Jabson said it is difficult to infer an explanation for these findings.

“We need to replicate our findings in a larger and more comprehensive sample to explore some of the causal or explanatory variables and to make sure that the result was not an artifact of the sample,” she said. “In addition, we agree with the IOM report that sexual orientation should be collected as a demographic variable in population-based health surveillance systems and cancer registries.”

Additional studies are warranted to explain the greater representation of individuals who self-identify as lesbian, gay and bisexual in cancer survivor clinical trials and potentially to identify ways to prevent and treat cancer in this community, according to Jabson.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In San Diego, Oct. 27-30:
(619) 358-6870

Socioeconomic Disadvantage Linked to Breast Cancer Tumor Disparity

registration@aacr.org () — Mon, 29 Oct 2012 12:00:00 GMT

ER- and PR-negative tumors were more common among black and Hispanic patients.
Non-Hispanic black and Hispanic patients lived in more disadvantaged areas.
Socioeconomic disadvantage accounted for half of the racial/ethnic disparity.

SAN DIEGO — Racial and ethnic disparities in breast tumor aggressiveness might be explained by social factors that influence the developing tumor and place those in disadvantaged groups at higher risk for aggressive breast cancer, according to data presented at the Fifth AACR Conference on The Science of Cancer Health Disparities, held here Oct. 27-30, 2012.

“There is a disparity in the biological aggressiveness of breast cancer,” said Garth H. Rauscher, Ph.D., associate professor of epidemiology at the University of Illinois at Chicago. “We tend to think about biological differences being due to differences in genes, but tumor biology can be affected by social or behavioral factors that are associated with socioeconomic status. Our study highlights the importance of the social environment in influencing tumor biology and ultimately influencing disparities.”

Rauscher and colleagues examined data from a population-based sample of 989 patients with a recent diagnosis of breast cancer (397 non-Hispanic whites, 411 non-Hispanic blacks and 181 Hispanics) from the Breast Cancer Care in Chicago Study. Patients were aged 30 to 79 years and had primary in situ or invasive breast cancer. A total of 742 patients consented to medical record abstraction and had medical record data available for estrogen receptor (ER) and progesterone receptor (PR) status.

Researchers established socioeconomic disadvantage using four measurements: individual income, individual education and two census tract measures of socioeconomic status — concentrated disadvantage and concentrated affluence.

Compared with 12 percent of non-Hispanic white patients, 29 percent of non-Hispanic black patients and 20 percent of Hispanic patients had ER- and PR-negative tumors. Non-Hispanic black and Hispanic patients were also more likely to have lower income and less education and to reside in more disadvantaged and less affluent neighborhoods. In addition, all four measures of socioeconomic disadvantage used in the study were strongly associated with ER/PR-negative status.

“It was interesting to see that the main finding remained unchanged regardless of the measure of socioeconomic status we used,” Rauscher said. “Patient levels of income and education, as well as neighborhood-level measures of socioeconomic status, were each associated with tumor biology. In each instance, lower socioeconomic status was associated with more aggressive breast cancers that lacked these hormone receptors.”

The study was funded by the National Institutes of Health Centers for Population Health and Health Disparities.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In San Diego, Oct. 27-30:
(619) 358-6870

Researchers Identify Biomarkers of Aggressive Behavior and Therapeutic Targets for Adult B-acute Lymphoblastic Leukemia

registration@aacr.org () — Mon, 29 Oct 2012 12:00:00 GMT

B-acute lymphoblastic leukemia is often an aggressive disease in adults.
Changes in DNA modification and packaging dictate aggressiveness.
Researchers identified possible indicators of those most at risk and potential therapeutic targets.

PHILADELPHIA — New insight into the aggressive behavior of certain adult B-acute lymphoblastic leukemias has provided researchers with a potential new prognostic biomarker and a promising new therapeutic target.

The research, conducted by Ari Melnick, M.D., associate professor of medicine and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell Medical College and a hematologist-oncologist at New York-Presbyterian Hospital/Weill Cornell Medical Center, and colleagues, was published in Cancer Discovery, a journal of the American Association for Cancer Research.

Although B-acute lymphoblastic leukemia is highly curable in children, the disease is usually fatal in adults, and researchers have yet to identify why this is the case. Part of the explanation for the poorer outcomes in adults is the higher frequency of genetic alterations associated with unfavorable prognosis.

In order to better understand why these genetic alterations are associated with poor outcomes, Melnick and colleagues studied 215 diagnostic specimens obtained from adults with B-acute lymphoblastic leukemia who were participating in a large Eastern Cooperative Oncology Group phase III clinical trial.

“We performed an integrative epigenomics study to decode the instructions that determine how these cells behave,” Melnick said. “The hope was that this would allow us to identify better survival biomarkers and new therapeutic targets.”

In many cancers, genetic alterations work in conjunction with epigenetic changes (changes in the way that DNA is modified and packaged) to promote cancerous behaviors. Looking at the B-acute lymphoblastic leukemia specimens, Melnick and colleagues found that many of the leukemias’ bad traits were a result of changes in the epigenetic code. In many cases, the epigenetic changes were directly linked to the proteins generated from the genetic alterations and could be used to identify key master regulators required for the leukemic cells to live, according to Melnick.

“For example, we found that a cell surface molecule called CD25 was an extremely powerful indicator of the presence of the most aggressive and fatal cases,” Melnick said.

The researchers also discovered that abnormal forms of the E2A and MLL proteins occurring in B-acute lymphoblastic leukemias directly reprogram epigenetic settings at their binding sites throughout the genome.

Most notably, the researchers found that mutant forms of MLL epigenetically reprogramed leukemia cells to express the powerful oncoprotein BCL6, and that BCL6 was required to maintain the proliferation and survival of the leukemia cells.

“We then designed inhibitors of BCL6 and showed that we could kill leukemia cells from patients enrolled in the clinical trial by blocking its function,” Melnick said.

Based on these results, the researchers plan to use CD25 as a biomarker to identify those patients who have the worst disease in the next set of clinical trials, and to tailor treatment appropriately. In addition, BCL6 inhibitors are currently being translated for use in humans, and they hope to develop clinical trials targeting BCL6 in MLL-rearranged leukemias.

“These results will ultimately lead to biomarkers that help guide treatment and to the development of therapies that will be more effective for patients with this aggressive form of leukemia,” Melnick said.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org

Minorities Most Likely to Have Aggressive Tumors, Less Likely to Get Radiation

registration@aacr.org () — Sun, 28 Oct 2012 12:00:00 GMT

Breast tumor aggressiveness increased receipt of chemotherapy, decreased adjuvant radiation utilization.
Adjuvant radiation still under-recommended.
Receiving chemotherapy decreased likelihood of radiation.

SAN DIEGO — Women with aggressive breast cancer were more likely to receive adjuvant chemotherapy, but at the expense of completing locoregional radiation therapy, according to recently presented data. This was especially true in minorities, who were the most likely to present with moderate- to high-grade and symptomatically detected tumors.

“Radiation treatment decreases the risk for breast cancer recurring and improves survival from the disease,” said Abigail Silva, M.P.H., Susan G. Komen Cancer Disparities Research trainee at the University of Illinois in Chicago, who presented the results at the Fifth AACR Conference on The Science of Cancer Health Disparities, held here Oct. 27-30, 2012.

Prior studies have shown that black and Hispanic women are less likely than white women to obtain radiation treatment when eligible, and this may partly explain racial/ethnic disparities in breast cancer outcomes, according to Silva.

To further examine factors in disparities in guideline-concordant radiation treatment, Silva and colleagues gathered interview and medical record data from a population-based study of patients with single invasive primary tumors, including 397 non-Hispanic whites, 411 non-Hispanic blacks and 181 Hispanics.

Of the patients who consented to medical record abstraction and were eligible for radiation treatment, 88 percent received a recommendation for radiation treatment and 93 percent of those patients accepted treatment. However, only 97 percent of patients who accepted treatment actually received radiation. Therefore, initiation occurred in only 79 percent of the initial population of women who were eligible for radiation treatment.

Data indicated that minority women were less likely to initiate radiation treatment compared with non-Hispanic white women. In addition, minority women were more likely to have moderate- to high-grade tumors and symptomatically detected tumors.

“We also found that patients who got chemotherapy were less likely to get radiation when they needed it,” Silva said. “Because minorities tended to have more aggressive breast cancer that more often required chemotherapy, this disproportionately affected them.”

Given these results, Silva and colleagues said clinicians may not be recommending guideline-concordant radiation treatment to all eligible patients.

“Indeed, we found that once a treatment recommendation was made, the vast majority of patients received treatment,” Silva said. “In addition, greater diffusion of gene expression profiling may improve cancer care, not only by reducing overuse of chemotherapy but by eliminating chemotherapy as a potential barrier to receipt of radiation.”

In the next phase of their research, Silva and colleagues plan to examine the role of mutable patient factors such as social support, cultural beliefs and provider mistrust, which may help explain the disparity in initiation of radiation treatment.

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In San Diego, Oct. 27-30:
(619) 358-6870

Language, Immigration Status of Hispanic Caregivers Impacted Care of Children With Cancer

registration@aacr.org () — Sun, 28 Oct 2012 12:00:00 GMT

Caregivers may delay seeking care if they are illegal immigrants.
Language was a barrier to caregivers fully understanding treatment risks.
Clinical trial consent process may not be adequate for Spanish-speaking caregivers.

SAN DIEGO — Language barriers and the immigration status of caregivers appear to impact the care of Hispanic children with cancer and affect the experience of the families within the medical system, according to data presented at the Fifth AACR Conference on The Science of Cancer Health Disparities, held here Oct. 27-30, 2012.

“Ensuring good communication with patients and their families is as important as the actual therapy we give, regardless of what language is spoken,” said Mark Fluchel, M.D., assistant professor in the department of pediatrics, division of hematology-oncology at the University of Utah Primary Children’s Medical Center in Salt Lake City. “However, for families for whom there is a language and possibly a cultural barrier, extra care needs to be taken to make sure we are providing the best care possible.”

Fluchel and his colleagues conducted a study among the primary caregivers of pediatric patients with cancer who were being treated at the University of Utah. Forty-six participants completed Spanish surveys and 323 completed English surveys. Caregivers evaluated various aspects of the child’s care, such as how soon after recognizing a symptom they sought care, how satisfied they were with the care, and whether the child was in a clinical trial. The survey also assessed financial, emotional and language barriers to the child’s care.

More than 65 percent of the Spanish-speaking respondents, defined as any caregiver who reported Spanish as their primary language, reported problems with their ability to speak English. Seventy percent of Spanish-speaking respondents reported that at least one member of their household had “undocumented” legal status. Thirteen percent reported avoiding or delaying care due to their immigration status.

When asked whether the child was enrolled in a clinical trial, 70 percent of Spanish-speaking caregivers and 40 percent of English-speaking caregivers reported that the child was enrolled in a clinical trial. However, when the researchers verified this information, they found that 32 percent of the Spanish-speaking and 12 percent of the English-speaking caregivers were incorrect about the child’s enrollment. Researchers interpreted these findings as the caregivers not fully understanding the informed consent process.

More Spanish-speaking caregivers reported feeling that the potential side effects of therapy were not explained well compared with English speakers. However, Spanish-speaking participants were more satisfied with their child’s overall care.

Among Spanish-speaking participants, 37 percent reported feeling not fully understood by the oncology staff, and 22 percent reported that they had falsely claimed understanding the oncology staff because they were embarrassed that they did not speak English. Eleven percent reported being uncomfortable asking for an interpreter, and 33 percent felt that their child would have received better care if English was their first language.

“As is the case with English speakers as well, we cannot assume that everything we say is understood,” Fluchel said. “The most important thing we can do is to quickly establish a trusting relationship with patients and their families and make sure they are comfortable asking for clarification. Once that kind of relationship is established, I think communication errors are less likely.”

# # #

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In San Diego, Oct. 27-30:
(619) 358-6870