Advances in Research on Fibroblast Growth Factor Receptors Alterations, Its Targeted Therapies and Companion Diagnosis

Cholangiocarcinoma is a group of rare and heterogeneous malignancies characterized by poor clinical outcomes. In spite of the increasing incidence of intrahepatic cholangiocarcinoma (ICC), few treatment options exist for patients with advanced disease due to its aggressiveness and highly complex nature. Driven by the advances in large-scale genetic sequencing technologies, potentially targetable genetic alterations have been identified in nearly half of the cholangiocarcinoma patients. Activation of the fibroblast growth factor receptor (FGFR) pathway, particularly those caused by fibroblast growth factor receptor 2 (FGFR2) rearrangements, is a common mechanism underlying ICC pathogenesis. Clinical trials of FGFR inhibitors have demonstrated promising results in advanced stage cholangiocarcinoma harboring FGFR2 rearrangements. This paper discusses the mutational landscape, detection methods and companion diagnosis of FGFR family genes, aiming to explore the oncogenic role and potential therapeutic value of FGFR in cholangiocarcinoma.