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Cholangiocarcinomas (CCAs) are a heterogenous group of epithelial malignancies originating at any level of the biliary tree and are subdivided according to their location into intrahepatic (iCCA) and extrahepatic (eCCA). This review provides an updated analysis of studies of genetic characterization of CCA at the level of gene mutation profiling, copy number alterations and gene expression, with definition of molecular subgroups and identification of some molecular biomarkers and therapeutic targets. With the development of genetic sequencing, several driver mutations have been identified and targeted as novel therapeutic approaches, including  FGFR2, IDH1, BRAF, NTRK, HER2, ROS,  and  RET . Furthermore, identification of the cellular and molecular structure of the tumor microenvironment has contributed to the development of novel therapies, such as tumor immunotherapy. Combination therapies of chemotherapy plus targeted molecules or immunotherapy are under evaluation and offer the unique opportunity to improve the outcomes of CCA patients with advanced disease.

The clinical value of identifying genetic abnormalities that can be targeted in cholangiocarcinomas