Pancreatic ductal adenocarcinoma: tumor microenvironment and problems in the development of novel therapeutic strategies

Abstract

Diagnosis and treatment of carcinoma of the exocrine part of the pancreas is a serious problem for modern medicine. Despite the identification of a large number of aberrant mutations in pancreatic ductal adenocarcinoma (PDAC), attempts to create effective therapeutic agents based on identified genetic or epigenetic variations have not been succesful. The role of the tumor microenvironment (TME) in tumor progression is currently a popular topic. Cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) are the main components of the tumor stroma and play an important role in the proliferation, invasiveness and metastasis of cancer. However, the mechanisms underlying the effect of CAFs and ECM on cancer progression are still unclear. Recent studies on stromal components and blockage of signaling pathways have brought some optimism to this area. New information on the role of TME will lead to the development of targeted therapies or combinations with modern chemotherapy for PDAC.

Keywords: CAF heterogeneity; Cancer-associated fibroblasts; Extracellular matrix; Pancreatic ductal adenocarcinoma; Stromal targeting; Tumor microenvironment.