Biliary tract cancers (BTCs) are rare tumours, most often diagnosed at an unresectable stage, associated with poor prognosis, with a 5-year survival rate not exceeding 10%. Only first- and second-line treatments are well codified with the combination of cisplatin-gemcitabine chemotherapy and immunotherapy followed by 5-FU and oxaliplatin chemotherapy, respectively. Many studies have shown that BTC, and more particularly intrahepatic cholangiocarcinoma (iCCA), have a high rate of targetable somatic alteration. To date, the FDA has approved several drugs. Ivosidenib targeting IDH1 mutations, as well as futibatinib and pemigatinib targetingFGFR2fusions, are approved for pre-treated advanced CCA. The combination of dabrafenib and trametinib are approved for BRAFV600E mutated advanced tumours, NTRK inhibitors entrectinib and larotrectinib for tumours bearing NTRK fusion and prembrolizumab for MSI-H advanced tumours, involving a small percentage of BTC in these three settings. Several other potentially targetable alterations are found in BTC, such asHER2mutations or amplifications orKRASG12C mutations and mutations in genes involved in DNA repair mechanisms. This review aims to clarify the specific diagnostic modalities for gene alterations and to summarize the results of the main trials and developments underway for the management of advanced BTC with targetable alterations.
胆道癌（BTCs）是一种罕见肿瘤，多数在确诊时已处于不可切除阶段，预后较差，五年生存率不超过10%。目前仅有一线和二线治疗方案较为明确，分别为顺铂-吉西他滨化疗联合免疫疗法，以及后续的5-氟尿嘧啶联合奥沙利铂化疗。多项研究表明，胆道癌（尤其是肝内胆管癌）存在较高比例的可靶向体细胞变异。截至目前，美国食品药品监督管理局已批准多种靶向药物：针对IDH1突变的艾伏尼布、针对FGFR2融合的福替尼替和培米替尼均已获批用于经治晚期胆管癌；达拉非尼联合曲美替尼获批用于BRAFV600E突变晚期肿瘤；NTRK抑制剂恩曲替尼和拉罗替尼适用于携带NTRK融合的肿瘤；帕博利珠单抗则用于MSI-H晚期肿瘤——但在这三类靶向治疗中，胆道癌患者仅占极小比例。胆道癌中还发现其他潜在可靶向变异，如HER2突变或扩增、KRASG12C突变以及DNA修复机制相关基因突变。本文旨在阐明基因变异的特异性诊断方法，并总结针对携带可靶向变异的晚期胆道癌的主要临床试验结果及治疗进展。
肿瘤(癌症)患者之家