胆管癌精准诊疗进展及前沿  

Advances in precision diagnosis and treatment of cholangiocarcinoma

作　　者：陈祯美 陈进宏 CHEN Zhenmei;CHEN Jinhong(Hepatobiliary Surgery,Department of General Surgery,Huashan Hospital&Cancer Metastasis Institute,Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学附属华山医院普外科肝胆外科中心,上海200040

出　　处：《中国临床药理学与治疗学》2025年第2期159-170,共12页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(82070655);上海市“科技创新行动计划”优秀学术带头人计划项目(22XD1400300)。

摘　　要：胆管癌(cholangiocarcinoma,CCA)是一种高侵袭性和异质性的胆道恶性肿瘤,其早期诊断困难、传统化疗疗效有限,预后较差。CCA在基因组、表观遗传学和分子水平上具有高度异质性,因此分子检测和靶向治疗在肿瘤诊疗中的作用愈发重要,已经成为精准肿瘤学时代不可或缺的一部分。下一代测序(next-generation sequencing,NGS)技术的发展促进了CCA肿瘤分子亚型和治疗靶点的研究,包括FGFR2融合/重排、IDH1突变和BRAF突变等。近年来,以TOPAZ-1和KEYNOTE-966为代表的2项III期临床研究确立了免疫治疗联合化疗在晚期胆管癌中的重要地位。CCA精准诊疗领域的探索已经初见成效,但目前仍处于探索阶段且面临诸多挑战。本文就近年来胆管癌的诊断、分子靶向治疗、免疫治疗的进展及其耐药机制的探索和新策略的开发进行综述。Cholangiocarcinoma(CCA)is a highly aggressive and heterogeneous biliary malignancy characterized by challenges in early diagnosis,limited efficacy of traditional chemotherapy,and poor prognosis.Due to its significant heterogeneity at the genomic,epigenetic,and molecular levels,molecular testing and targeted therapy have become increasingly important in CCA management,forming an integral part of the era of precision oncology.The development of next-generation sequencing(NGS)has advanced research into the molecular subtypes and therapeutic targets of CCA,including FGFR2 fusions/rearrangements,IDH1 mutations,and BRAF mutations.Recently,two phase III clinical trials,TOPAZ-1 and KEYNOTE-966,have established the pivotal role of immunotherapy combined with chemotherapy in advanced CCA.While precision diagnosis and treatment in CCA have shown promising progress,this field remains in its exploratory phase and faces numerous challenges.This review summarizes recent advancements in the diagnosis,molecular targeted therapy,immunotherapy,resistance mechanisms,and the development of novel strategies for CCA.

关 键 词：胆管癌 靶向治疗 免疫治疗 精准诊疗 

分 类 号：R735.8[医药卫生—肿瘤]