MODULATING TUMOR MICROENVIRONMENT IN PANCREATIC ADENOCARCINOMA BY USING A COMBINATION OF FOCAL ADHESION KINASE, AUTOPHAGY AND CHECKPOINT INHIBITORS

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with very low survival, and is resistant to most of the chemotherapeutic regimens. A combination therapy using focal adhesion kinase inhibitors and autophagy inhibitors along with checkpoint immimotherapy may be useful to prolong survival in pancreatic cancer patients. FAK inhibitors target the stroma causing tumor stasis and autophagy inhibitors target both the stroma and tumor cells, preventing tumor growth. Checkpoint inhibitors will target the tumor cells and allow the immune system to more efficiently attack them. FAK, autophagy and checkpoint inhibitors will be administered alone and in combination to KPC mice which will be monitored for tumor growth and histology. Combining focal adhesion kinase inhibitors and autophagy inhibitors may have a synergistic effect on the tumor and adding checkpoint immunotherapy may regress the tumor and prolong survival in PDAC patients.