Grant: Operating Grant

Tumor heterogeneity is largely thought to arise from different gene mutation events. Mounting evidence also suggests that distinct tumor-initiating cell types, or cells of origin, may also contribute to heterogeneity in prostate and breast cancer. However, little is known about the factors that contribute to heterogeneity in pancreatic cancer. In addition, it is difficult to associate variables like cellular origin with heterogeneity solely using patient samples. To address whether cellular origin and gene mutations initiate tumor heterogeneity, we created mouse genetic tools that allow us to target distinct pancreatic cancer-initiating mutations specifically to pancreatic ductal or acinar cells. In the proposed research, we will use these genetically engineered mouse models to examine how cellular and molecular mechanisms affect generation of pancreatic cancer heterogeneity. The knowledge generated by this research will aid identification of molecular markers that can reproducibly identify PDAC subtypes with distinct therapeutic responses and clinical outcomes.