Project 2: Functions of cell death selection during early pancreatic cancer development

Coworkers: to be appointed, Jenny Dewes

Pancreatic ductal adenocarcinoma (PDAC) is the cancer carrying the most common KRAS mutation, G12D, at the highest frequency. We have previously shown that murine TRAIL-receptor (mTRAIL-R) can unexpectedly promote KRAS-driven PDAC and metastasis (see von Karstedt et al. Cancer Cell 2015). To now test the hypothesis that the expression of mTRAIL-R led to apoptotic selective pressure, possibly selecting for more aggressive sub-variants of KRASG12D-driven pancreatic intraepithelial neoplasia (PanIN) which more easily progress to PDAC, we will characterise the role of cell death in PanIN-to-PDAC progression via pancreas-specific deletion studies of cell death inducers. Importantly, this will identify mechanisms of early PDAC progression through selection which we aim to utilize for the development of novel treatment strategies which turn selection into eradication. This project is funded through the Max-Eder Programme of the Deutsche Krebshilfe.