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.
