PHILADELPHIA — A new molecular pathway involving the gene ZNF365 has been identified and abnormalities in that pathway may predict worse outcomes for patients with breast cancer, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

“Genomic instability is an increased tendency for abnormal changes in DNA, like the addition of extra copies of chromosomes, DNA breaks and mutations,” said Ji-Hye Paik, Ph.D., assistant professor in the Department of Pathology and Laboratory Medicine at Weill Cornell Medical College in New York, N.Y. “Because these genetic abnormalities increase the chances for developing a tumor, it is fundamentally important to understand the molecular basis of genomic instability in cancer for prognosis and therapy.”

Telomeres are segments at the end of the chromosome that protect the chromosome from deterioration. As the length of the telomeres shortens, they activate cell death, mediated by the tumor suppressor gene, p53. This process is critical in the suppression of cancer, and dysfunctional telomeres can cause chromosomal abnormalities and cancer.
 
Using cells designed to be cancer-prone because of defective telomeres, Paik and colleagues demonstrated that p53 activates ZNF365 to maintain genomic stability. The researchers found that cells deficient in ZNF365 showed signs of incomplete doubling of DNA, causing abnormal cell division and unequally divided chromosomes. They concluded that because ZNF365 promotes the timely resolution of cell division, its loss led to an abnormal number of chromosomes called aneuploidy, which is implicated in many diseases including cancer.

“Our study is the first to demonstrate molecular mechanisms underlying the p53–ZNF365–telomere pathway and to show how alterations in this pathway may lead to increased cancer risk,” said Paik. “Understanding this pathway provides novel therapeutic opportunities for cancers.”

To understand the role of ZNF365 in cancer, Paik and colleagues used data available from The Cancer Genome Atlas (TCGA) and analyzed the expression of ZNF365 in 49 triple-negative breast cancers (TNBCs) — the most aggressive form of breast cancer — and 300 non-TNBCs. They found that expression of ZNF365 was lowest in TNBCs, and it remained high in non-TNBCs.

Using data from a larger cohort of 2,978 women from TCGA, the researchers also found that among women who had a 10-year, relapse-free survival, those with a high expression of ZNF365 had a 26 percent higher survival advantage. Further, when the researchers analyzed for the presence of ZNF365 in a tissue microarray containing 18 normal breast tissues, 141 TNBCs and 145 non-TNBCs, ZNF365 was present in normal breast tissues and non-TNBCs, but its expression declined in TNBCs.

According to Paik, this study is the first to determine the expression of ZNF365 in different types of breast cancers, and because it predicts disease prognosis, ZNF365 may be a potential biomarker for patient stratification.

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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 18,000 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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PHILADELPHIA — The American Association for Cancer Research (AACR) congratulates Charles L. Sawyers, M.D., president of the AACR and Brian J. Druker, M.D., fellow of the AACR Academy and former member of the AACR Board of Directors, on receiving the 2013 Taubman Prize for Excellence in Translational Medicine Science in recognition of their outstanding contributions to the treatment of chronic myeloid leukemia (CML).

The A. Alfred Taubman Medical Research Institute, based at the University of Michigan Medical School in Ann Arbor, presents the $100,000 prize annually to acknowledge work in the crucial field of translational medical science by clinician-scientists who have transformed laboratory discoveries into clinical applications.

“On behalf of the American Association for Cancer Research, I extend sincere congratulations to our President Dr. Charles Sawyers and to Dr. Brian Druker on their receiving this pre-eminent award,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “They are both internationally respected thought leaders in translational and clinical research, and their passionate commitment to accelerating progress has yielded molecularly targeted therapies that have benefited tens of thousands of patients worldwide. Their dedication to further improving the lives of patients is renowned, and they are truly deserving of this prestigious accolade.”

The institute is honoring Druker, director of the Oregon Health and Science University Knight Cancer Institute in Portland, for his work on the development of imatinib (Gleevec), and Sawyers, chair of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center in New York, N.Y., for his research on imatinib resistance, which led to the development of second-generation drugs.

These researchers turned CML from a fatal cancer into a highly treatable one. Prior to imatinib’s 2001 approval, bone marrow transplantation was the only treatment option and was associated with poor outcomes. Now, patients receiving imatinib have a five-year survival rate of about 90 percent. In addition, imatinib is effective for the treatment of other cancers, including gastrointestinal stromal tumors. Sawyers’ research on the molecular underpinnings of imatinib resistance led to the development of second-generation drugs.  

Sawyers and Druker will jointly present the keynote address and receive the Taubman Prize trophy at the Taubman Institute’s 2013 annual symposium on Oct. 11 in Ann Arbor.

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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 18,000 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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PHILADELPHIA — Genetic variations, known as single nucleotide polymorphisms (SNPs), in or near the genes ZNF423 and CTSO were associated with breast cancer risk among women who underwent prevention therapy with tamoxifen and raloxifene, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

Women who have the favorable variations of these two SNPs are more likely to respond to prevention therapy, according to this study. Women who have the unfavorable variations of these SNPs may not benefit from prevention therapy, and they have a five-fold increased risk of developing breast cancer.

“The recent guidelines by the U.S. Preventive Services Task Force emphasize that selective estrogen receptor modulator (SERM) therapy with tamoxifen and raloxifene can lower a woman’s risk for developing breast cancer. But about 50 women have to be exposed to the treatment and side effects to prevent a single case of breast cancer,” said James N. Ingle, M.D., professor of oncology at the Mayo Clinic in Rochester, Minn.

“Our findings are important, because for the first time, we discovered genetic factors that could be used to select women who should be offered the drugs for prevention. Also of substantial importance is that we have discovered new information on how tamoxifen and raloxifene work to prevent breast cancer.”

Ingle and his colleagues at the Mayo Clinic, along with researchers at the National Surgical Adjuvant Breast and Bowel Project (NSABP) in Pittsburgh, Pa., and the RIKEN Center for Genomic Medicine in Tokyo, Japan, conducted a genome-wide association study involving 592 patients who developed breast cancer while on SERM therapy and 1,171 matched controls. They selected participants from the 33,000 women enrolled in the NSABP P-1 and P-2 breast cancer prevention trials.

He and his colleagues analyzed participants’ DNA using the Illumina Human610-Quad BeadChip to identify variations in their genetic makeup. They identified two SNPs that were most relevant to breast cancer risk, one in the gene ZNF423, and the other near the gene CTSO.

“Our discovery is a major step toward truly individualized prevention of breast cancer. Findings from our study provide clear direction as to which women are likely and which are unlikely to benefit from tamoxifen or raloxifene,” said Ingle. “The best chance we have of decreasing the burden of breast cancer is to prevent it in the first place. Our findings provide the basis for a reinvigoration of research efforts in breast cancer prevention.”

The researchers conducted further experiments using breast cancer cell lines harboring either the most common variation or the less common variation of the SNPs. They found that in cells with the most common variation of the SNPs, estrogen increased expression of both ZNF423 and CTSO, as well as expression of BRCA1, a gene related to breast cancer risk. Estrogen did not increase expression of these genes in cells that had the less common form of the SNPs.

When tamoxifen or raloxifene were added to estrogen, there was a striking reversal in the patterns of expression of ZNF423 and BRCA1. In cells with the less common ZNF423 SNP, expression of ZNF423 and BRCA1 rose dramatically. This reversal in expression patterns provides a potential explanation for the decreased occurrence of breast cancer in women undergoing SERM therapy who carry this SNP.

In addition, the researchers found that the different forms of the ZNF423 and CTSO SNPs predicted the odds for developing breast cancer while undergoing SERM therapy: Women who had the favorable variations of both the SNPs had the lowest risk and women who had the unfavorable variations of both the SNPs had a more than five-fold relative increased risk for developing breast cancer.

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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 18,000 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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PHILADELPHIA — The American Association for Cancer Research (AACR) has issued a call for nominations for its 2013 AACR Award for Outstanding Achievement in Cancer Prevention Research.  

The award, formerly the AACR-Prevent Cancer Foundation Award for Excellence in Cancer Prevention Research, is bestowed upon a scientist from anywhere in the world for seminal contributions to the field of cancer prevention. The research for which the individual is recognized must have been conducted in basic, translational, clinical, epidemiological or behavioral science in cancer prevention research. Furthermore, these studies must have had not only a major impact on the field, but must also have stimulated new directions in this important area.

The recipient of the award will receive a $5,000 honorarium and present a 50-minute lecture at the 12th Annual AACR International Conference on Frontiers in Cancer Prevention Research. The conference will be held Oct. 27-30, 2013, in National Harbor, Md.

Last year’s award was presented to Jack Cuzick, Ph.D., John Snow professor of epidemiology, Wolfson Institute of Preventive Medicine, Queen Mary University of London. Cuzick was recognized for his outstanding contributions to cancer prevention research in breast, cervical, bowel and prostate cancers.

• Deadline for nominations: June 20, 2013
• For more information, contact Monique P. Eversley at awards@aacr.org or visit www.aacr.org/ScientificAwards.

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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 18,000 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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Lauren.Riley@aacr.org

PHILADELPHIA — The American Association for Cancer Research (AACR) has issued a call for nominations for its 2013 Distinguished Lectureship on the Science of Cancer Health Disparities, funded by the Susan G. Komen Foundation.

The AACR Distinguished Lectureship on the Science of Cancer Health Disparities is awarded to an investigator whose novel work has had or may have a far-reaching impact on the etiology, detection, diagnosis, treatment or prevention of cancer health disparities. This work may involve any discipline in biomedical research including basic, translational, clinical or epidemiological studies.

The recipient of this year’s award will receive a $5,000 honorarium and present a 45-minute lecture at the Sixth Annual AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. The conference will be held Dec. 6-9, 2013, in Atlanta, Ga.

Last year’s award was presented to Claudia R. Baquet, M.D., Ph.D., associate dean for policy and planning, professor of medicine and director of the National Bioethics and Health Disparities Research Center, University of Maryland School of Medicine, Baltimore. She delivered a lecture titled, “Advancing the Science of Cancer Health Disparities: The Case for Public Trust, Bioethics, Research Literacy and Biospecimen Science.”

• Deadline for nominations: June 20, 2013
• For more information, contact Monique P. Eversley at awards@aacr.org or visit www.aacr.org/ScientificAwards.

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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 18,000 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

PHILADELPHIA — Novel abnormalities in the FGFR gene, called FGFR fusions, were identified in a spectrum of cancers, and preliminary results with cancer cells harboring FGFR fusions suggested that some patients with these cancers may benefit from treatment with FGFR inhibitor drugs, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

FGFR genes are receptors that bind to members of the fibroblast growth factor family of proteins and play a role in key biological processes of a human cell. Because of a chromosomal abnormality, this gene sometimes fuses with another gene and forms a hybrid, or a gene fusion, resulting in a gene product with an entirely different function, causing cancers.

“We found targetable FGFR gene fusions across a diverse array of cancer types. Although rare for any individual cancer type, if found in an individual patient, these fusions are likely a major driver of that patient’s cancer,” said Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology at the University of Michigan in Ann Arbor. “We were surprised to find so many different FGFR fusions in so many different cancers.

“This study demonstrates the benefit of broad-based sequencing efforts in personalized oncology. It has the potential to identify novel, rare mutations that are ‘actionable’ therapeutic targets,” Chinnaiyan added. “Such advances in sequencing technology facilitate rational precision therapies for individuals with late-stage cancer.”

The Michigan Oncology Sequencing Program (MI-ONCOSEQ) facilitates integrative sequencing analysis of tumors from patients with advanced cancers. More than 100 patients have been enrolled since 2011. Through the project, researchers analyze the mutational landscape of each patient’s tumor and suggest clinical trials or approved drugs that might be appropriate for that patient, according to Chinnaiyan.

He and his colleagues identified novel fusions of the gene FGFR2 in the tumors of four patients recruited to MI-ONCOSEQ. Of these four patients, two had metastatic tumors of the bile duct; the third had metastatic breast cancer and the fourth had metastatic prostate cancer.

To further analyze whether FGFR fusions are present across different types of cancers, the researchers extended their assessment and analyzed data generated from an internal cohort of 322 patients, as well as from a large cohort of 2,053 patients recruited to The Cancer Genome Atlas. They identified several distinct FGFR fusions in nine different types of cancers, including bladder cancer, brain cancer and lung cancer.

Chinnaiyan and colleagues then conducted studies using cancer cells and found that the different FGFR fusion proteins all seemed to drive cancer cell proliferation by activating FGFR signaling. The researchers were able to inhibit proliferation of the cells in vitro using the FGFR inhibitors PD173074 and pazopanib. In addition, they injected mice with human cancer cells and found that the tumors grown in mice could be inhibited with PD173074.

One of the four patients whose metastatic bile duct tumor failed to respond to conventional chemotherapy was recruited to an FGFR inhibitor trial, and he is currently undergoing treatment, according to Chinnaiyan.

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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 18,000 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

Editor’s Note: A downloadable image of this issue’s cover is available here.

PHILADELPHIA — The Spring 2013 issue of Cancer Today, a publication of the American Association for Cancer Research (AACR), features poignant stories on surviving cancer a second time and increasing participation of African-American patients in clinical trials, as well as a touching photo essay on young breast cancer patients.  

Published quarterly by the AACR, Cancer Today is an authoritative resource for cancer patients, survivors, and their family members and friends. In every issue, Cancer Today offers information and inspiration to help readers face the challenges of diagnosis, treatment, survivorship or caregiving.

This issue of Cancer Today includes “When Cancer Rings Twice,” which outlines the steps cancer survivors can take to reduce their risks of a second cancer diagnosis, something that will occur in one out of every six people diagnosed with cancer. “Changing the Face of Clinical Trials” examines the efforts underway to increase participation among African-American patients, who are currently underrepresented in clinical trials.

Writer Cynthia Ryan and fashion photographer David Jay capture the struggles of young breast cancer patients facing financial and family issues, in addition to their illness and treatment in a photo essay.

To read these stories, go to Cancer Today, or follow the magazine on Facebook at facebook.com/CancerToday and Twitter at twitter.com/CancerTodayMag. Media are welcome to use information from Cancer Today; however, we ask that you cite the source.

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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 18,000 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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PHILADELPHIA — A subset of colorectal cancers responds to anti-epidermal growth factor receptor (anti-EGFR) therapies, but develops resistance within months. Among cancers that develop resistance to anti-EGFR therapy, some showed overexpression of a gene called MET, according to a study published in the June issue of Cancer Discovery, a journal of the American Association for Cancer Research. Preliminary data published in this study showed human tumors with MET amplification, grown in mice, responded to MET inhibitor drugs.

The MET gene is known to be amplified in about 10 percent of colorectal cancers, and is associated with worse prognosis.

The paper was also presented as part of an oral session at the 2013 American Society of Clinical Oncology Annual Meeting.

“Our studies provide evidence that colorectal cancer resistance to anti-EGFR therapies can be driven by MET gene amplification,” said Alberto Bardelli, Ph.D., associate professor in the Department of Oncology at the University of Torino in Italy. “But what is more exciting is that we were able to detect these amplifications in the blood.”

A subset of metastatic colorectal cancers responds to the anti-EGFR drugs cetuximab and panitumumab, but almost always develops resistance within several months of the initiation of therapy, according to Bardelli. Mutations in genes related to EGFR signaling, including KRAS, BRAF and NRAS, account for about 60 percent of the cases that develop resistance; the cause of resistance in tumors without these mutations is unknown.

“Unfortunately, patients whose tumors recur after anti-EGFR therapy are out of further options currently,” said Bardelli. “The possibility that we can identify those who have MET amplification using a blood test is exciting because they might be treated with MET inhibitors.”

Bardelli and his colleagues analyzed tumors from seven patients who developed resistance subsequent to anti-EGFR therapy, and identified three who did not have the previously known mutations. Using next-generation sequencing, they demonstrated amplification of the MET gene in these three tumor samples.

Blood samples collected at regular intervals during treatment with anti-EGFR therapy until relapse were available for two of the three patients. The researchers were able to detect MET amplification in the blood, and they demonstrated it occurred prior to relapse. The ability to detect MET amplification in blood provides a noninvasive, highly sensitive method for monitoring and predicting drug resistance and tumor recurrence, according to Bardelli.

Using “xenopatients” — patient-derived, drug-resistant colorectal cancers grafted and grown in mice — the researchers identified a novel, biologically distinct subset of tumors that were resistant to anti-EGFR drugs and did not have alterations in KRAS, BRAF or NRAS but carried MET amplification. The researchers further confirmed the overexpression of the MET gene and MET protein in these tumors using special techniques called fluorescent in situ hybridization and immunohistochemistry.

As a next step, the researchers tested the efficacy of the clinically approved MET inhibitor crizotinib in two xenopatients. According to Bardelli, a MET inhibitor in combination with an anti-EGFR drug caused maximum antitumor activity and sustained response in both xenopatients. He added that this provided proof of concept that MET inhibitors, alone or in combination with anti-EGFR therapies, offer novel therapeutic opportunities.

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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 18,000 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

PHILADELPHIA — A newly developed, single-step Raman spectroscopy algorithm has the potential to simultaneously detect microcalcifications and enable diagnosis of the associated breast lesions with high precision, according to data published in Cancer Research, a journal of the American Association for Cancer Research.

“Nearly 1.6 million breast biopsies are performed and roughly 250,000 new breast cancers are diagnosed in the Unites States each year,” said Ishan Barman, Ph.D., postdoctoral fellow at the Massachusetts Institute of Technology in Cambridge and the study’s lead author. “If 200,000 repeat biopsies were avoided, even by a conservative estimate, the U.S. health care system could save $1 billion per year.”

X-ray mammography is currently the only accepted routine screening method for early detection of breast cancer, but it cannot accurately distinguish whether microcalcifications (microscopic areas of calcium accumulation) are associated with benign or malignant breast lesions, according to Barman. Most patients, therefore, undergo core needle biopsy to determine if the microcalcifications are associated with malignancy, but the technique fails to retrieve microcalcifications in about 15 to 25 percent of patients. This results in nondiagnostic or false-negative biopsies, requiring the patient to undergo repeat, often surgical biopsy.

According to the researchers, the newly developed algorithm exhibited positive and negative predictive values of 100 percent and 96 percent, respectively, for the diagnosis of breast cancer with or without microcalcifications. The algorithm also showed an overall accuracy of 82 percent for classification of the samples into normal, benign or malignant lesions.

“There is an unmet clinical need for a tool that could minimize the number of X-rays and biopsy procedures. This tool could shorten procedure time; reduce patient anxiety, distress and discomfort; and prevent complications such as bleeding into the biopsy site after multiple biopsy passes,” said Barman. “Our study demonstrates the potential of Raman spectroscopy to simultaneously detect microcalcifications and diagnose associated lesions with a high degree of accuracy, providing real-time feedback to radiologists during the biopsy procedures.”

The researchers used a portable clinical Raman spectroscopy system to obtain Raman spectra from breast tissue biopsy specimens of 33 women. They collected Raman spectra from 146 tissue sites within the samples, including 50 normal tissue sites, 77 lesions with microcalcifications and 19 lesions without microcalcifications. Notably, they acquired all spectra within 30 minutes of sample removal.

Barman and colleagues fitted the obtained spectra into a model that identifies the different type and texture of various components of the breast tissue. They then developed a single-step Raman algorithm to distinguish normal breast tissue, breast cancer with and without microcalcifications, and other benign breast lesions including fibrocystic change and fibroadenoma.

In addition, the majority of breast cancers diagnosed using the one-step Raman algorithm were ductal carcinoma in situ, the most common lesion associated with microcalcifications, which is a challenge to diagnose using existing methods, according to Barman.

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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 18,000 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

• Frequent history of heartburn elevated risk for throat and vocal cord cancers.
• Use of antacids lowered risk.
• Further studies are needed to confirm the protective effect of antacids.

PHILADELPHIA — Frequent heartburn was positively associated with cancers of the throat and vocal cord among nonsmokers and nondrinkers, and the use of antacids, but not prescription medications, had a protective effect, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Previous studies examining gastric reflux and cancers of the head and neck have generated mixed results,” said Scott M. Langevin, Ph.D., postdoctoral research fellow at Brown University in Providence, R.I. “Most of those studies had either few numbers of cases or they were not adjusted for confounding factors. Ours is a large, population-based study with robust parameters that strongly suggests gastric reflux, which causes frequent heartburn, is an independent risk factor for cancers of the pharynx (throat) and larynx (vocal cord).”

Langevin and his colleagues identified 631 patients from a large group of individuals enrolled in a population-based, case-control study in the greater Boston area. Of the 631 participants, 468 had throat cancer and 163 had cancers of the vocal cord. An additional 1,234 individuals matched for age and gender with no prior history of cancer were recruited using town records to serve as controls for the study.

All participants completed a questionnaire on their history of heartburn, smoking and drinking habits, family history of cancer and sociodemographic information. Because some head and neck cancers are caused by infection with human papillomavirus 16 (HPV 16), the researchers tested for the presence of antigens to HPV 16 viral proteins in the blood of all participants.

Langevin and his colleagues found that among participants who were neither heavy smokers nor heavy drinkers, a history of frequent heartburn was linked to a 78 percent increased risk for cancers of the throat and vocal cord. They also found that among those who had frequent heartburn, taking antacids, but not prescription medications or home remedies, had a protective effect, with a 41 percent reduced risk for cancers of the throat and vocal cord. The protective effect of antacids was consistent, irrespective of the participants’ smoking or drinking status, HPV 16 status or tumor site.

“Additional studies are needed to validate the chemopreventive effects of antacids among patients with frequent heartburn,” said Langevin. “The identification of gastric reflux as a risk factor for throat and vocal cord cancers, however, may have implications in terms of risk stratification and identification of high-risk patients.”    

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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 18,000 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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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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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 18,000 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

• 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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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 18,000 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