Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA–Associated Pancreatic Cancer in the Clinical and Preclinical Setting

glBRCA pancreatic ductal adenocarcinoma (PDAC) has a favorable response to platinum/PARP inhibition. However, most patients develop resistance. Additional treatment options for this unique subpopulation are needed. We generated model systems in PDXs and an ex vivo system (EVOC) that faithfully recapitulate these specific clinical scenarios as a platform to investigate the mechanisms of resistance for further drug development. In this study, we aimed to recapitulate the glBRCA PDAC population spectrum of responses to platinum and PARPi therapy, to explore the genomic and clinical features that may lead to different responses, and to investigate the mechanisms of resistance.