Molecular Targets in Biliary Carcinogenesis and Implications for Therapy

Abstract

Abstract Biliary tract cancers (BTCs) encompass a group of invasive carcinomas, including cholangiocarcinoma (intrahepatic, perihilar, or extrahepatic), and gallbladder carcinoma. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. The latest recommendation is to treat advanced or metastatic disease with gemcitabine and cisplatin, although chemotherapy has recorded modest survival benefits. Comprehension of the molecular basis of biliary carcinogenesis has resulted in experimental trials of targeted therapies in BTCs, with promising results. This review addresses the emerging role of targeted therapy in the treatment of BTCs. Findings from preclinical studies were reviewed and correlated with the outcomes of clinical trials that were undertaken to translate the laboratory discoveries. Implications for Practice: Biliary tract cancers are rare. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. Median overall and progression-free survival are 12 and 8 months, respectively. Because chemotherapy has recorded modest survival benefits, targeted therapies are being explored for personalized treatment of these cancers. A comprehensive review of targeted therapies in biliary tract cancers was undertaken to present emerging evidence from laboratory and/or molecular studies as they translate to clinical trials and outcomes. The latest evidence on this topic is presented to clinicians and practitioners to guide decisions on treatment of this disease.