Personalized Medicine in Advanced Cholangiocarcinoma

Abstract

Journal Publication Date: August 6, 2020 Personalized medicine is the new-generation concept of managing cancer, which primarily focuses on the development of targeted therapies blocking specific cellular pathways that potentiate the tumorigenesis and identify people that respond best. The combination of gemcitabine and a platinum agent, remains the first-line therapy in advanced cholangiocarcinoma. Thus far, there are no specific guidelines on the next step in the care of patients who progressed on, or could not tolerate, the first-line therapy. However, a better knowledge of molecular pathogenesis and advancements in the development of targeted therapy offers hope that we may improve outcomes in advanced cholangiocarcinoma. Among the newly discovered molecular alterations, targeting isocitrate dehydrogenase (IDH1/2) mutations, fibroblast growth factor receptor 2 (FGFR2) fusions, RAS-MAPK pathway activation, BRCA1/2 mutations, NTRK fusions, and human epidermal growth factor receptor 2 (HER2), hold great promise for improving the future management of cholangiocarcinoma. In tumors with high microsatellite instabilities or mismatch repair deficiencies irrespective of programmed death ligand (PD-L) 1 expression, immunotherapy, alone or in combination with targeted agents and chemotherapy, are currently being evaluated. This review article details the potential targetable molecular pathways and future directions in implementing personalized medicine in this dismal cancer.