Microenvironment in determining chemo-resistance in pancreatic cancer: Neighborhood matters

Abstract

Every year, nearly 300,000 people are diagnosed with pancreatic cancer worldwide, and an equivalent number succumb to this disease. One of the major challenges of pancreatic cancer that contributes to its poor survival rates is the development of resistance to the standard chemotherapy. Heterogeneity of the tumor, the dense fibroblastic stroma, and the aggressive biology of the tumor all contribute to the chemoresistant phenotype. In addition, the acellular components of the tumor microenvironment like hypoxia, stress pathways in the stromal cells, and the cytokines that are secreted by the immune cells, have a definitive role in orchestrating the chemoresistant property of the tumor. In this review, we systematically focus on the role played by the different microenvironmental components in determining chemoresistance of pancreatic tumors.

Keywords: Chemoresistance; Hypoxia; Metabolism; Tumor initiating cells.

Figure 1

A schematic displaying the role of the microenvironment in pancreatic adenocarcinomas (TME). The TME includes the immune cells (tumor associated macrophages (TAM) and neutrophils); stroma (extra cellular matrix (ECM) and cancer associated fibroblasts (CAF)); cancer stem cells (CSC) and non-CSC; in a hypoxic environment. Further, CSCs contain inactive mitochondria, higher levels of drug efflux channels, increased glucose uptake and lactate export.