Previous studies have identified different subtypes of pancreatic cancer, but those studies were not entirely able to include a molecular analysis of the large amount of surrounding stroma that is intermixed with both normal and cancerous pancreatic tissue.

Blind source separation allowed for separating the normal from the cancerous tissue and the stroma. Researchers were then able to examine gene expression patterns for each type in tissue samples from five institutions.


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They analyzed 145 primary and 61 metastatic tumors, 17 cell lines, as well as 46 normal pancreatic samples. They also analyzed 88 samples of normal, non-cancerous tissue outside of the pancreas.

Dr. Yeh said this study helps make sense of researchers’ conflicting findings about stroma in which it can either promote or be a barrier to tumor growth.

The basal-like subtype was linked to worse outcomes for patients. And only 44% of patients with the basal-like subtype lived for 1 year after surgery compared to a 70% survival for patients with the classical subtype. Basal-like tumors also trended towards a better response to adjuvant therapy.

Dr. Yeh said knowing that a tumor is aggressive may point to treating the whole body first with neoadjuvant therapy as opposed to just trying to remove the tumor with surgery at the outset.

The investigators hope to launch clinical trials to determine how these newly identified subtypes may be used to predict response to therapy.

The basal-like subtype is molecularly similar to basal tumors in bladder and breast cancers, which respond to therapies differently than other tumor subtypes. The question now is will this hold true for pancreatic cancers.

Wafik S. El-Deiry, MD, PhD, FACP, deputy cancer center director for translational research and professor of medical oncology at Fox Chase Cancer Center in Philadelphia, PA, said this study answers many key questions. Pancreatic cancer has a major so-called “activated stromal cell” made up of tissue cells that interact with the tumor cells to help the tumors grow.

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“What this paper does is provide detailed molecular information about the different components of a pancreatic tumor and its stroma. This helps us understand how this activated stroma promotes the tumors to grow, and helps us appreciate that not all pancreatic tumors are the same,” Dr. El-Deiry told Cancer Therapy Advisor.

“Eventually this type of detailed understanding of the heterogeneity and make-up of pancreatic tumors as it relates to patient survival will help focus efforts on developing new treatments.”

Reference

  1. Moffitt RA, Marayati R, Flate EL, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. [published online ahead of print September 7, 2015]. Nature Genetics. doi: 10.1038/ng.3398.