Targeting BRCA-mutant biliary tract cancer: Current evidence and future perspectives

Biliary tract cancers (BTCs) are aggressive tumors of the biliary system, which are often diagnosed at the advanced stage with a dismal prognosis. Among BTC patients, germline or somatic breast cancer-related gene 1/2 (BRCA1/2) mutation has been reported and the use of poly(ADP-ribose) polymerase inhibitor (PARPi) has achieved a certain effect, with no obvious severe side effects. The frequencies and mutated types of BRCA1/2 in advanced BTCs vary among studies. BRCA1 and BRCA2 play distinct roles in the development of BTC regardless of age or gender difference. Surprisingly, some BTC patients with germline BRCA mutation can achieve better therapeutic effects than those with a somatic mutation, and patients who carry BRCA mutation are more likely to benefit from immunotherapy alone or in combination. Herein, we provide an overview of the targeted therapies in BRCA-mutant BTCs, with a particular focus on the differences between germline and somatic BRCA1/2 mutations, as well as review the current status and perspectives.

Automated summary

Biliary tract cancers (BTCs) are aggressive tumors of the biliary system that are often diagnosed at an advanced stage with a poor prognosis. BRCA1/2 mutations have been reported in BTC patients, and treatment with PARP inhibitors has shown some effectiveness without severe side effects. The frequencies and types of BRCA1/2 mutations in advanced BTCs vary among studies. Differences in the therapeutic effects and response to immunotherapy between germline and somatic BRCA mutations have been observed.