Patient-derived xenograft models of BRCA-associated pancreatic cancers

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. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

PDAC is a dismal disease with poor overall survival rates, often diagnosed at advanced stages. The most clinically meaningful subtype from PDAC genomic classification has unstable genomes and inactivation of DNA damage repair genes. Treatment with olaparib has been approved for some advanced PDAC patients with BRCA mutations, but resistance remains a challenge.