Deciphering the role of stroma in pancreatic cancer.

Abstract

This review intends to describe recent studies on pancreatic tumor-associated stroma and potential opportunities and limitations to its targeting. One of the defining features of pancreatic cancer is extensive desmoplasia, or an inflammatory, fibrotic reaction. Carcinoma cells live in this complex microenvironment which is comprised of extracellular matrix (ECM), diffusible growth factors, cytokines and a variety of nonepithelial cell types including endothelial cells, immune cells, fibroblasts, myofibroblasts and stellate cells. In addition to the heterogeneity noted in the nonneoplastic cells within the tumor microenvironment, it has also been recognized that neoplastic cancer cells themselves are heterogeneous, and include a subpopulation of stem-cell like cells within tumors termed cancer stem cells. Due to the failure of current therapeutics to improve outcomes in patients with pancreatic cancer, new therapeutic avenues targeting different components of the tumor microenvironment are being investigated. In this review article, we will focus on recent studies regarding the function of the tumor stroma in pancreatic cancer and therapeutic treatments that are being advanced to target the stroma as a critical part of tumor management. Recent studies have shed new light on the contribution of the pancreatic cancer fibroinflammatory stroma to pancreatic cancer biology. Additional studies are needed to better define its full contribution to tumor behavior and how to best understand the optimal ways to develop therapies that counteract its pro-neoplastic properties.