Genomic Alterations and Clinical Implications in Biliary Tract Cancer

Abstract

Cholangiocarcinoma is one of the cancers frequently observed in Asia, including Japan. In Japan, its 5-year survival rate remains below 15%, making it one of the most lethal cancers after pancreatic cancer. Although the molecular and genetic characteristics of cholangiocarcinoma had long been insufficiently studied, recent large-scale genomic analyses by multiple research groups have revealed that driver genes exhibit considerable diversity depending on tumor location and individual cases. In addition to FGFR2 fusion genes and IDH1 mutations-already approved as therapeutic targets in Japan and the United States-other actionable driver genes such as HER2, KRAS, and BRAF have been identified. Consequently, treatment strategies for cholangiocarcinoma are now undergoing a major shift toward personalized medicine based on genomic alterations. This article provides an overview of the driver alterations identified in cholangiocarcinoma and the current status of therapeutic drug development targeting these abnormalities.