Recent advances in understanding cancer-associated fibroblasts in pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a devastating disease with a poor survival rate. It is resistant to therapy in part due to its unique tumor microenvironment, characterized by a desmoplastic reaction resulting in a dense stroma that constitutes a large fraction of the tumor volume. A major contributor to the desmoplastic reaction are cancer-associated fibroblasts (CAFs). CAFs actively interact with cancer cells and promote tumor progression by different mechanisms, including extracellular matrix deposition, remodeling, and secretion of tumor promoting factors, making CAFs an attractive target for PDA. However, emerging evidences indicate significant tumor-suppressive functions of CAFs, highlighting the complexity of CAF biology. CAFs were once considered as a uniform cell type within the cancer stroma. Recently, the existence of CAF heterogeneity in PDA has become appreciated. Due to advances in single cell technology, distinct subtypes of CAFs have been identified in PDA. Here we review recent updates in CAF biology in PDA, which may help develop effective CAF-targeted therapies in the future.