摘要
肝内胆管癌(intrahepatic cholangiocarcinoma,肝内胆管癌)是一种少见的消化道恶性肿瘤,起病隐匿且缺乏筛查手段,分子靶向治疗对这一高度异质性的疾病具有较明显的治疗效果。目前取得较好研究进展的治疗靶点包括表皮生长因子受体(epidermal growth factor receptor,EGFR)、血管内皮生长因子(vascular endothelial growth factor,VEGF)及其VEGF受体(VEGFreceptor,VEGFR)、异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)、成纤维细胞生长因子受体(fibroblastgrowthfactor receptor,FGFR)、热休克蛋白90(heat shock protein 90,HSP90)和C-ROS癌基因1(C-ROS oncogene 1,ROS1)等。其中,FGFR2和IDH1基因突变几乎仅见于肝内胆管癌,部分针对上述靶点的药物取得了显著的临床疗效,并且通过了适应证的审批。FGFR的激酶结构域极易产生门控位点突变,导致肝内胆管癌出现靶向药物获得性耐药。TAS-120和HSP90抑制剂等药物具有逆转肝内胆管癌耐药的前景,需要在临床前研究及临床试验中进一步验证其疗效和安全性。本文就近年肝内胆管癌分子靶向治疗研究的进展进行综述,对肝内胆管癌靶向药物耐药问题及解决方法进行讨论和展望。
Intrahepatic cholangiocarcinoma(iCCA)is a rare gastrointestinal malignant tumor,which has an insidious onset and lacks screening methods.Molecular targeted therapy has a good therapeutic effect on this highly heterogeneous disease.Therapeutic targets that have made quite good research progress include epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF)and its receptor(VEGFR),isocitrate dehydrogenase(IDH),fibroblast growth factor receptor(FGFR),heat shock protein 90(HSP90),C-ROS oncogene 1(ROS1),etc.Among them,FGFR 2 and IDH 1 gene mutations are found in iCCA exclusively.Some drugs that target these targets have achieved significant clinical efficacy and approved by the administration.Gate keeper mutations are prone to emerge in the kinase domain of FGFR,resulting in the acquired drug resistance of iCCA.Drugs such as TAS-120 and HSP90 inhibitors have the prospect of reversing iCCA resistance,instead,their efficacy and safety need to be further verified in preclinical and clinical research.In this paper,the research progress of iCCA molecular targeted therapy is reviewed,and the difficulties and solutions of iCCA targeted therapy drug resistance are discussed and prospected.
作者
段诣
胡粟衔
杨旭鹏
武志华
段友容
孙颖
DUAN Yi;HU Suxian;YANG Xupeng;WU Zhihua;DUAN Yourong;SUN Ying(State Key Laboratory of Oncogenes and Related Genes,Shanghai Cancer Institute,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200032,China)
出处
《肿瘤》
CAS
CSCD
北大核心
2022年第11期750-760,共11页
Tumor
基金
国家自然科学基金面上项目(81972886,82172736)
关键词
肝内胆管癌
分子靶向治疗
研究进展
Intrahepatic cholangiocarcinoma
Molecular targeted therapy
Research progress
作者简介
Correspondence to:孙颖,E-mail:ysun@shsci.org
