Dense surrounding tissue can block drugs from reaching pancreatic cancer tumors, but it also can help prevent the cancer from spreading. New research led by members of the UNC Lineberger Comprehensive Cancer Center helps explain the conflicting role of the surrounding tissue, known as stroma.
[Photo: A UNC study describes two new subtypes of stroma and two subtypes of pancreatic cancer tumors. The findings could help physicians tailor treatments to individual patients, an advancement particularly important for a disease that has a five-year survival rate of only 7 percent. Photo by Argonne National Laboratory]
Ms. Lindsay A. Williams, UNC Lineberger researcher and doctoral student in epidemiology at UNC Gillings School of Global Public Health, is a co-author of the study, which examined molecular characteristics and found two subtypes of pancreatic cancer stroma.
Published September 7 in the journal Nature Genetics, the study describes both new subtypes of stroma and two subtypes of pancreatic cancer tumors. The findings could help doctors tailor treatments to individual patients, an advancement particularly important for a disease that has a five-year survival rate of only seven percent.
“Right now, we still treat pancreatic cancers as one entity, while for some other cancers, we personalize treatment based on an individual patient’s tumor genetics or other characteristics,” said the study’s senior author Dr. Jen Jen Yeh, a UNC Lineberger member and associate professor and the vice chair for research in the UNC School of Medicine’s department of surgery. “We believe these results will set the groundwork for future clinical trials, allow treatments to be assigned based on the subtypes, and guide the development of new therapies.”
The study reveals the most rigorously validated classification system for pancreatic ductal adenocarcinoma to date. Previous studies, including one in 2011 led by Dr. Eric A. Collisson, assistant professor at the University of California at San Francisco School of Medicine, have identified subtypes of pancreatic cancer. However, researchers in the current study believe those attempts were confounded by the large amount of surrounding stroma that is intermixed with both normal and cancerous pancreatic tissue.
To solve that problem, UNC Lineberger researchers used a mathematical approach led by Dr. Richard Moffitt, a postdoctoral research associate at UNC Lineberger, to separate the tissue. The approach, called blind source separation, allowed researchers to separate normal tissue from cancerous tissue and from the stroma. Researchers then were able to examine gene expression patterns for each type in tissue samples from five different institutions. They analyzed 145 primary and 61 metastatic tumors, 17 cell lines, as well as 46 normal pancreatic samples and 88 samples of normal, non-cancerous tissue outside of the pancreas.
“The issue is that pancreatic cancer is a particularly difficult cancer to analyze because of its confounding stroma, so we needed to marry the right data analysis technique to the right problem,” Dr. Moffitt said.
The researchers uncovered two subtypes of pancreatic stroma that they called “normal” and “activated.” Patients with the activated subtype had worse survival outcomes.