Patient-derived xenograft models of BRCA-associated pancreatic cancers

[Display omitted] •Pancreatic cancer patients demonstrate a limited response to chemotherapy.•Pancreatic cancer subtype: unstable tumors co-segregated with inactivation of DNA damage repair genes e.g. BRCA1/2.•BRCA-associated PDAC demonstrates a response to platinum chemotherapy/PARP inhibitors, however resistance develops.•BRCA-associated PDAC PDX model recapitulating the clinical scenario, i.e., sensitivity or resistance to treatment.•BRCA-associated PDAC PDX models may potentially identify novel therapeutic strategies for tumors resistant to treatment. Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease. The majority of patients diagnosed at an advanced, metastatic stage, and poor overall survival rates. The most clinically meaningful subtype obtained from PDAC genomic classification is represented by unstable genomes, and co-segregated with inactivation of DNA damage repair genes, e.g., Breast cancer 1/2 (BRCA1/2). The FDA and EMA has recently approved olaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor, as a maintenance strategy for platinum-sensitive advanced PDAC patients with BRCA mutations. However, susceptibility to treatment varies, and resistance may develop. Resistance can be defined as innate or acquired resistance to platinum/PARP-inhibition. Patient-derived xenograft (PDX) models have been utilized in cancer research for many years. We generated a unique PDX model, obtained from BRCA-associated PDAC patients at distinct time points of the disease recapitulating the different clinical scenario. In this review we discuss the relevant PDX-derived models for investigating BRCA-associated PDAC and drug development.