Pancreatic cancer patients face tough odds, given that the disease has a five-year survival rate of less than 9 percent. Now, researchers at the University of Pittsburgh Medical Center (UPMC) and the University of Pittsburgh School of Medicine have reported the publication of a study in pancreatic ductal adenocarcinomas (PDAC) that looked into the role of comprehensive genomic profiling in treatment and clinical research. The study characterized the genome of 3,594 pancreatic tumor samples from patients around the world, provided by collaborators at Cambridge, Mass.-based Foundation Medicine Inc.

Siraj Ali, senior director of clinical development at Foundation, emphasized the distinct challenge patients with the disease and their families face. "There are advances happening in, say, lung cancer and melanoma, which is great. But I think the advocacy groups, like PanCAN [the Pancreatic Cancer Action Network], will tell you, they'll take any hint of progress," he told BioWorld.

Part of the problem for these patients is that the disease often is identified late, meaning the tumors are inoperable. For some, it may be possible to shrink the tumor with existing chemotherapy drugs; however, with that disease, 75 percent of patients die within a year of diagnosis, meaning time is of the essence.

To help in that endeavor, researchers from the UPMC and the University of Pittsburgh School of Medicine have sought genetic signatures that could be used to better match drugs to patients and for early detection. In addition, the teams found supporting evidence for heritable genes – including some in the BRCA family – 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, oncologist at UPMC Hillman Cancer Center and associate professor of medicine at Pitt.

"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, 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."

Cysts

Beyond shrinking tumors with personalized chemotherapy, another way to increase pancreatic cancer survival rates is through increased screening of cysts, explained Singhi. However, pancreatic cysts are incredibly common, and not all lead to cancer.

Singhi and colleagues already developed Pancreaseq, a clinical molecular test, to evaluate common pancreatic cysts and identify those cases that could progress to cancer. Now Singhi and Bahary's newly discovered biomarkers can be added to the Pancreaseq platform.

Their findings were published in Gastroenterology in an article titled "Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers," which appeared online March 2, 2019.

Foundation's involvement

"We had a proposal submitted to us a couple of years back," Ali told BioWorld when asked how the collaboration with academic institutions came about. "This study, as it is now, really describes the most common kind of pancreatic cancer," which represents about 85 percent of cases. "Due to our unique position as a very high-volume central laboratory, we had the largest genomic experience with [PDAC]," he added.

Of note, the company said this is likely the largest study in pancreatic cancer done using comprehensive genomic profiling to identify a broad set of genomic alterations, as well as potential therapeutic targets, for this disease.

When asked to provide additional detail about his company's specific role, he noted that part of Foundation's business is helping physicians who are looking to have their patients tested with a genomic profiling assay. "Pancreatic patients, unfortunately, are very sick or have a very poor prognosis. Standard-of-care treatment . . . has limited efficacy. Genomic profiling by a central lab like ours . . . can identify alterations in genes, which suggest a benefit from either a targeted [therapy] or immunotherapies."

There are broader hopes for the study and its results. "[It] is intended as a resource for the broader community. We'll be thinking about how can we follow up on some of the insights that were generated here either in terms of basic cancer biology or in terms of implications for care for advanced pancreatic cancer patients. At the same time, I think we hope that the broader community involved in the care of pancreatic cancer patients looks at this and forms hypotheses."

When asked whether the company would work with the Pittsburgh-based team in other cancers, Ali noted the company has an ongoing collaboration with the teams. "We have done similar collaborations with other institutions, and I think we'd continue to be open to such studies, particularly when they're hypothesis-driven or involve unexpected observations about cancer patients that might be enlightened by genomic results."