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Cholangiocarcinoma (CCA) is an uncommon malignancy originating from epithelial cells of the biliary tract. Regardless of the site of origin within the biliary tree, CCAs are generally aggressive with a poor survival. Surgical resection remains the only chance for cure, yet a majority of patients are not surgical candidates at presentation. Unfortunately, systemic therapies are often ineffective and complicated by side effects. As such, more effective targeted therapies are required in order to improve survival. Genetic analysis of CCA has allowed for a better understanding of the genomic landscape of CCA. Isocitrate dehydrogenase ( IDH ) and fibroblast growth factor receptor ( FGFR ) mutations have emerged as the most promising molecular targets for CCA. Inhibitors of  IDH  and  FGFR  have proven to have therapeutic benefit with an acceptable safety profile. However, patients often develop resistance rendering the therapy ineffective. Understanding the molecular pathways of  IDH  and  FGFR  may lead to a better understanding of the mechanisms of resistance. Thus, novel therapies may be developed to improve the efficacy of these therapies. Developing novel biomarkers may improve patient selection and further enhance effectiveness of targeted therapies.

Developments in FGFR and IDH inhibitors for cholangiocarcinoma therapy