Biliary tract cancers: current knowledge, clinical candidates and future challenges

Noor-ul-Ain Tariq,1,2 Mairéad G McNamara,1,2 Juan W Valle1,2 1Faculty of Biomedicine and Health Sciences, Division of Cancer Sciences, University of Manchester, Manchester M13 9NT, UK; 2Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK Abstract: Biliary tract cancers (BTCs) are rare with poor prognosis. Due to the advent of genomic sequencing, new data have emerged regarding the molecular makeup of this disease. To add to the complexity, various subtypes also harbor a varied genetic composition. The commonly mutated genes associated with this cancer are KRAS, EGFR, IDH, FGFR and BAP1. Various clinical studies are looking at targeting these genetic mutations. Another therapeutic area of note is the potential for the use of immunotherapy in patients with BTC. Although BTC may be a result of chronic inflammation, this does not necessarily translate into increased immunogenicity. This literature review discusses the diverse molecular and immune-related pathways in patients with BTC and their potential therapeutic implications. Keywords: biliary tract cancer, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, genome sequencing, molecular targets, immunotherap