PITTSBURGH, March 4 - Pancreatic cancer is a grim diagnosis, with a five-year survival rate of less than 9 percent. To improve those odds, researchers at UPMC and the University of Pittsburgh School of Medicine sought genetic signatures in the largest study of its kind that could be used to better match drugs to patients and for early detection.
The study, published in the journal Gastroenterology, involved sifting through the genomes of thousands of tumors, sampled from all over the world. In 17 percent of cases, there was a genetic flag that indicated the tumor should be susceptible to existing chemotherapy drugs. The researchers also found supporting evidence for heritable genes, including some in the BRCA family associated with breast cancer, that can predispose whole families toward pancreatic cancer.
"People have been looking for such markers for a long time, and our study shows that it's possible to break pancreatic cancer patients into different treatment buckets," said senior author Nathan Bahary, M.D., Ph.D., oncologist at UPMC Hillman Cancer Center and associate professor of medicine at Pitt.
One reason why pancreatic cancer is so deadly is that the majority of patients often are identified late in their disease course and frequently present with inoperable tumors at the time of diagnosis. For some of these patients, it may be possible to shrink the tumor with existing chemotherapy drugs, but in a disease where 75 percent of patients die within a year of diagnosis, time is of the essence, and unfortunately, there's no way to know in advance which patients will respond to which drugs.
"Every pancreatic cancer is different, and performing molecular profiling of each patient's tumor could help determine the best treatment options," said lead author Aatur Singhi, M.D., Ph.D., surgical pathologist at UPMC and assistant professor of pathology at Pitt. "Rather than blindly giving patients the same chemotherapy, we want to tailor a patient's chemo to their tumor type. A one-size-fits-all approach isn't going to work. Therefore, we would like to make molecular profiling standard-of-care for patients with pancreatic cancer."
Singhi and Bahary's study characterized the genome of 3,594 pancreatic tumor samples from patients around the world, provided by collaborators at Foundation Medicine.
"We believe that this is the largest study in pancreatic cancer conducted using comprehensive genomic profiling to identify a broad set of genomic alterations, and ultimately, therapeutic targets, in this difficult-to-treat disease," said Siraj Ali, M.D., Ph.D., senior director of clinical development at Foundation Medicine.
Besides shrinking tumors with personalized chemotherapy, another way to increase pancreatic cancer survival rates is through increased pancreatic cysts screening, Singhi said, but the problem is that pancreatic cysts are incredibly common, and not all lead to cancer.
Previously, Singhi and colleagues developed a clinical molecular test known as PancreaSeq to evaluate common pancreatic cysts and identify which cases may progress to cancer. Now Singhi and Bahary's newly discovered biomarkers can be added to the PancreaSeq platform, already being used by several institutions, including UPMC.
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Additional authors on the study include Ben George, M.D., from the Medical College of Wisconsin; Joel Greenbowe, Ph.D., Jon Chung, Ph.D., James Suh, M.D., Alexa Schrock, Ph.D., Vincent Miller, M.D., Jeffrey Ross, M.D., and Siraj Ali, M.D., Ph.D., from Foundation Medicine Inc.; Anirban Maitra, M.B.B.S., and Javle Milind, M.D., from University of Texas MD Anderson Cancer Center; Samuel Klempner, M.D., and Andrew Hendifar, M.D., from Cedars-Sinai Medical Center; Talia Golan, M.D., from Tel Aviv University; and Randall Brand, M.D., Amer Zureikat, M.D., and Somak Roy, M.D., from UPMC and Pitt.
This research was funded by the Pancreatic Cancer Action Network, the National Pancreas Foundation and the Sky Foundation.
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About UPMC
A $19 billion world-renowned health care provider and insurer, Pittsburgh-based UPMC is inventing new models of patient-centered, cost-effective, accountable care. UPMC provides more than $900 million a year in benefits to its communities, including more care to the region's most vulnerable citizens than any other health care institution. The largest nongovernmental employer in Pennsylvania, UPMC integrates 87,000 employees, 40 hospitals, 700 doctors' offices and outpatient sites, and a 3.5 million-member Insurance Services Division, the largest medical insurer in western Pennsylvania. As UPMC works in close collaboration with the University of Pittsburgh Schools of the Health Sciences, U.S. News & World Report consistently ranks UPMC Presbyterian Shadyside on its annual Honor Roll of America's Best Hospitals. UPMC Enterprises functions as the innovation and commercialization arm of UPMC, and UPMC International provides hands-on health care and management services with partners around the world. For more information, go to UPMC.com.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.
Journal
GASTROENTEROLOGY