Targeting P2X7 Receptor Antagonists for Prevention of Pancreatic Cancer

The overall objective of this task order is to evaluate specific inhibitors of P2X7R for pancreatic cancer prevention in preclinical models. Specifically, the contractor shall test 2 such inhibitors (AZ10606120 (HAQDT) and A438079) by first establishing the optimal dose and maximal tolerated dose (MTD) in mice and then assess the pancreatic cancer prevention efficacy in p48Cre/+-LSL-KrasG12D/+ transgenic mouse model of pancreatic cancer. In addition, test the modifications in inflammasome signal pathways and critical biomarkers of pharmacodynamic efficacy, which will be applicable to early-phase clinical studies.