Personalized Treatment for BRCA Mutated Pancreatic Cancer

Despite advancements in surgical techniques, radiation, and medical therapies, the 5-year survival rate remains below 10%. Recently, the genomic landscape of pancreatic ductal adenocarcinoma (PDAC) has been extensively studied, leading to the identification of BRCA mutations, currently recognized as a target for the development of novel personalized therapies. Alterations in germline BRCA and PALB2 are detected in approximately 5–9% of patients with PDAC and can result in homologous repair deficiency (HRD), and consequently, accumulation of double-stranded breaks. In patients with germline BRCA mutations, platinum-based chemotherapies and poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) are efficacious treatment options that may confer survival benefits. Olaparib is currently indicated for maintenance therapy in metastatic PDAC, BRCA mutated whose disease does not progress after first-line platinum-based chemotherapy. Strategies combining therapies are currently under investigation. This review discusses the rationale for gBRCAm testing in patients with PDAC and its clinical implications. We also summarize recent literature on cisplatin-based chemotherapy and PARP inhibitors in patients with BRCA-mutated PDAC.