Search

Winston Wong,1 Alexander G Raufi,1,2 Rachael A Safyan,1 Susan E Bates,1,3 Gulam A Manji1,4 1Division of Hematology and Oncology, Columbia University Medical Center and New York Presbyterian Hospital Herbert Irving Pavilion, New York, NY 10032, USA; 2Division of Hematology-Oncology, Lifespan Cancer Institute, Warren-Alpert Medical School of Brown University, Providence, RI, USA; 3Division of Hematology and Oncology, James J. Peters Veterans Affairs Medical Center, The Bronx, NY 10468, USA; 4Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center and New York Presbyterian Hospital Herbert Irving Pavilion, New York, NY 10032, USACorrespondence: Winston WongDivision of Hematology and Oncology, Columbia University Medical Center and New York Presbyterian Hospital, Milstein Hospital Building, 6 Garden North, Rm 6-435 177 Fort Washington Ave, New York, NY 10032, USATel +646-675-8254Email ww2539@cumc.columbia.eduAbstract: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease to treat. Despite advances in surgical techniques, radiation, and medical therapies, the 5-year survival rate remains below 9%. Over the past decade, the genomic landscape of PDAC has been well studied and BRCA mutations have emerged as a target for the development of more effective therapies. Alterations in germline BRCA and PALB2 are detected in approximately 5– 9% of patients with PDAC and can lead to homologous repair deficiency (HRD). PDAC with HRD is more susceptible to cytotoxic agents, such as platinum salts and topoisomerase inhibitors, that cause DNA damage. Furthermore, PARP inhibitors have emerged as an effective non-cytotoxic approach to treating HRD-PDAC. In addition to BRCA and PALB2, germline mutations in other genes involved in the homologous DNA repair pathway – such as ATM and RAD51 – are potential targets, as are patients with the “BRCAness” phenotype and somatic mutations in the DNA repair pathway. Given the clinical implications of germline mutation related HRD in PDAC, universal germline testing is now recommended. In this review, we will discuss current and emerging biomarkers for HRD in PDAC, treatments, and the challenges associated with them.Keywords: pancreas cancer, clinical trials, BRCA