Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

SIMPLE SUMMARY: Tumors from pancreatic cancer contain many types of cells (such as immune cells and fibroblasts) in addition to the cancer cells. Using targeted drugs to disrupt interactions between these cells which can support cancer cell growth, invasion, and immune suppression has become an important area of exploration in the pancreatic cancer field. This review describes new drugs designed to modulate interactions between cancer cells and other cell types in the tumor and discusses the initial clinical trials testing these novel therapeutics in pancreatic cancer patients. ABSTRACT: Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Here, new therapeutic strategies designed to modulate the cancer-associated fibroblast and immune compartments of pancreatic ductal adenocarcinomas are described and clinical trials of novel therapeutics are discussed. Continued advances in our understanding of the pancreatic cancer tumor microenvironment are generating stromal and immune-modulating therapeutics that may improve patient responses to anti-tumor treatment.