Clinical response of pancreatic cancer bearing a germline BRCA2 p.I3169M fs*48 variant for platinum-based drug and PARP inhibitor.

Abstract

Pancreatic cancer is a malignancy with a high mortality rate, accounting for 37 000 people annually in Japan. It is rarely diagnosed in a resectable state, and effective medicines for its advanced stage are scarce. Some pancreatic cancer is hereditary, and ~10% have germline mutations of Breast cancer 1/2 (BRCA1/2). BRCA1/2 are key molecules involved in homologous recombination to repair DNA double-strand break. Platinum-based drugs and poly Adenosine diphosphate ribose (ADP) ribose polymerase inhibitors that induce synthetic lethality would be theoretically effective in patients with loss-of-function mutations in BRCA1/2. Strictly speaking, some discrepancy between the pathogenicity of BRCA1/2 and their drug sensitivity might be expected. Hence, we report that platinum-based anticancer agents and poly ADP ribose polymerase inhibitors were effective against pancreatic cancer bearing BRCA2 p.I3169M fs*48.