Determining if cysts develop into cancer could lead to preventive surgeries – Zoo House News

A Duke Health research team has identified a number of biomarkers that could help distinguish whether cysts on the pancreas are likely to develop into cancer or remain benign.

The finding, published online March 17 in the journal Science Advances, marks an important first step toward a clinical approach to classifying pancreatic lesions at highest risk for cancer and potentially allowing their removal before they spread spread.

If successful, the biomarker-based approach could remove the biggest obstacle to reducing the likelihood of developing pancreatic cancer, which is on the rise and is notorious for growing silently before it is often discovered incidentally on abdominal scans.

“Even when pancreatic cancer is detected in its earliest stages, it has almost always shed cells throughout the body and the cancer will come back,” said senior author Peter Allen, MD, chief of the Division of Surgical Oncology in the Department of Surgery at Medical Faculty of Duke University.

“So we shifted our focus to these precancerous cysts known as intraductal papillary mucinous neoplasms, or IPMNs,” Allen said. “Most IPMNs will never lead to pancreatic cancer, but by distinguishing which ones progress we create a way to prevent the development of an incurable disease.”

Allen and colleagues used a sophisticated molecular biology tool called digital spatial RNA profiling to pinpoint specific areas of the cyst with high- and low-grade areas of abnormal cell growth.

Previous methods for characterizing IPMNs were less precise and failed to identify particularly accurate markers of cancer risk. However, digital spatial profiling allows researchers to select individual groups of cells for analysis. This allowed Duke researchers to identify a variety of genetic mutations that both promote and potentially suppress the development of pancreatic cancer.

The team also identified markers for distinguishing between the two leading variants of IPMN and found different markers for defining a third common variant that generally results in a less aggressive disease.

“We found very different markers for high-grade cell abnormalities as well as for slow-growing subtypes,” Allen said. “Our work now focuses on finding it in the cyst fluid. If we can identify these unique markers in the cyst fluid, it could provide the basis for a protein biopsy that would tell us if we should remove the cyst before cancer develops and spreads.”

Allen said current diagnostic strategies — including clinical, radiographic, laboratory, endoscopic, and cytological analyzes — have an overall accuracy of about 60%.

“Pancreatic cancer is on the rise and, if current trends continue, will become the second leading cause of cancer death in the United States in the next few years,” Allen said, noting that it’s unknown what’s driving the cancer’s increasing prevalence.

He said some studies suggest inflammation plays a role. A clinical trial at Duke, led by Allen, is testing whether anti-inflammatory therapy could reduce the development of cancer in patients with IPMN.

In addition to Allen, study authors include Matthew K. Iyer, Chanjuan Shi, Austin M. Eckhoff, Ashley Fletcher, and Daniel P. Nussbaum.

The study received financial support from the National Cancer Institute (RO1 CA182076).