Review of IDH mutations and potential therapies for intrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) is an aggressive malignancy that arises from the biliary tract. Currently, the first-line therapy for advanced CCA is gemcitabine and cisplatin. However, 5-year survival remains low. It has become abundantly clear that a “one size fits all” approach no longer applies to the treatment of individual cancers, given the large amount of tumor heterogeneity. As such, research in recent years has focused on developing effective targeted therapies through genetic profiling of CCA tumors. IDH1 and IDH2 mutations are commonly found in intrahepatic CCA (ICCA). IDH mutations prevent hepatic progenitor cell differentiation and result in the persistence of progenitor-like and stem cells. These are more prone to alterations that promote tumor initiation. As such, IDH has been identified as a promising target for ICCA treatment. We herein review the role of IDH mutations in ICCA development, recent data for IDH inhibitors in ICCA treatment, and challenges within the field of targeted therapy for ICCA.