Therapeutic targets in the pancreatic adenocarcinoma microenvironment: past challenges and opportunities for the future

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related mortality, with cytotoxic chemotherapy still the mainstay of treatment. Beyond effective therapeutic agents alone, successful drug delivery is paramount. In PDAC, the tumor microenvironment represents a physical barrier that limits in vivo drug delivery and efficacy. In this review, we highlight therapeutic targets in the tumor microenvironment, focusing on past challenges and opportunities for the future. Targets discussed include the Hedgehog pathway, angiogenesis, hyaluronic acid, cancer-associated fibroblasts and associated cytokines, among others. Despite the obstacles in successfully recapitulating promising lab results to practice-changing clinical results, many important lessons have been learned to improve clinical trial design within a highly engaged and motivated scientific community. These collaborative efforts and the collective optimism will continue to propel the momentum forward to overcome these barriers and ultimately improve patient outcomes.

Keywords

Pancreatic cancer / PDAC / tumor microenvironment / pancreatic stroma

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