肝内胆管癌分子靶向治疗的机制探索与临床应用现状OA

Intrahepatic cholangiocarcinoma(ICC)is a highly heterogeneous malignancy comprising 10%-15%of primary liver cancers with its global incidence continuing to rise and the 5-year survival rate remaining below 20%.Conventional chemotherapy offers limited efficacy,making molecularly targeted therapy the central research focus in this field.Well-established therapeutic targets—including IDH1/2 gene mutations,FGFR2 gene fusions,NTRK gene fusions,and HER2 amplification/overexpression—have corresponding approved agents,providing precision treatment options for patients with specific molecular subtypes.B-Raf proto-oncogene serine/threonine-protein kinase(BRAF),SMAD family member 4(SMAD4),BRCA1-associated protein 1(BAP1),AT-rich interactive domain-containing protein 1A(ARID1A),vascular endothelial growth factor receptor(VEGFR),and mesenchymal-epithelial transition factor(MET)represent potential therapeutic targets that drive ICC progression through key signaling pathways,including RAS-MAPK,PI3K-AKT,and TGF-β.Relevant inhibitors and combination regimens have demonstrated preliminary efficacy in early-phase clinical trials.This review systematically summarizes the molecular mechanisms of core therapeutic targets,the clinical application of approved agents,and research advances in emerging targets for ICC-directed therapy,with the aim of providing a reference for precision treatment of ICC.