Brcaness in Biliary Tract Cancer: A New Prognostic and Predictive Biomarker?

Abstract

Cholangiocarcinoma (CCA) is a rare malignancy with a very poor prognosis. Considering that most cases of CCA are diagnosed at a locally advanced stage and the standard of care for advanced CCA remains suboptimal, new prognostic and predictive biomarkers must be developed to improve the management and survival of patients diagnosed with CCA regardless of disease stage. According to recent studies, 20% of biliary tract cancers exhibit the BRCAness phenotype, meaning that these tumors do not have germline mutations in BRCA but share phenotypic traits with tumors that possess hereditary BRCA mutations. Therefore, screening for these mutations in CCA patients is beneficial to predict tumor sensitivity and response to DNA-damaging chemotherapy such as platinum agents.

Austrian tricentric real-life analysis of molecular profiles of metastatic biliary tract cancer patients

“…Firstly, biomarkers such as IDH1 and FGFR2 fusions are currently investigated in clinical trials in first-line settings which means that -in case that the trials meet the endpointthe patients will receive front-up a targeted therapy (41)(42)(43). The second reason is that new predictive biomarkers are tested in different trials, including biomarkers for predicting the effectiveness of immunotherapies, such as ATM, ATR, BRCA1, BRCA2, FANCA, and POLE (44,45). Last, but not least, new emergent therapies will likely be a gamechanger in the BTC management, particularly KRAS inhibitors (46,47).…”