LAUSR

ABSTRACT Introduction The treatment landscape of biliary cancers is rapidly changing. Inhibitors against the actionable targets FGFR and IDH1 are now being included in the treatment guidelines of multiple countries for patients with advanced cholangiocarcinoma. However, there remains an unmet need in identifying the mechanisms of resistance and treatment strategies involving possible tumor sequencing. Areas covered In this review article, we address clinical trials evaluating FGFR, IDH, BRAF and HER2 inhibitors in advanced cholangiocarcinoma. We also review the mechanisms of resistance described thus far and approaches to overcome them. Articles selected for this review were based on reported studies indexed in PubMed (2010–2022). Expert opinion Precision medicine in biliary cancers has already been incorporated into the treatment landscape of the disease in many countries. Fusions of FGFR2 and mutations in IDH1 are the first drivers with targetable treatments approved in these cancers. HER2 and BRAF would be the next drivers with possible tumor-agnostic or cholangiocarcinoma-specific approvals. The advent of ctDNA could improve the accessibility of sequencing and recruitment in these clinical trials. However, limitations of detecting fusions should be considered and addressed in these platforms.