肝细胞癌仑伐替尼耐药机制与新治疗策略  

Lenvatinib in hepatocellular carcinoma:resistance mechanism and novel treatment strategy

作　　者：奇卓然 杜晓静 杨毕伟 曹鑫 夏景林 QI Zhuo-ran;DU Xiao-jing;YANG Bi-wei;CAO Xin;XIA Jing-lin(Liver Cancer Institute,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Gastroenterology,Minhang Hospital,Fudan University,Shanghai 201199,China;Biomedical Research Center,Zhongshan Hospital,Fudan University,Shanghai 200032,China;The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang,China;Department of Gastroenterology,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院肝癌研究所,上海200032 [2]复旦大学附属闵行医院消化内科,上海201199 [3]复旦大学附属中山医院实验研究中心,上海200032 [4]温州医科大学附属第一医院,温州325000 [5]复旦大学附属中山医院消化内科,上海200032

出　　处：《中国临床医学》2023年第2期335-342,共8页Chinese Journal of Clinical Medicine

基　　金：国家自然科学基金(81972233)。

摘　　要：仑伐替尼是继索拉非尼之后FDA首次批准的晚期肝细胞癌(hepatocellular carcinoma,HCC)一线用药,临床研究显示其疗效与索拉非尼相当,并在某些方面更具优势。然而,伴随仑伐替尼的大规模使用,近年来其临床耐药问题也引起高度关注。表皮生长因子受体(EGFR)激活、成纤维细胞生长因子受体1(FGFR1)过表达及HCC中肿瘤干细胞出现等为仑伐替尼耐药的重要原因。面对仑伐替尼耐药,一些创新性研究也取得了积极进展,如仑伐替尼联合免疫检查点抑制剂经临床试验证实具有良好疗效,成为新兴的HCC治疗策略。本文总结了近年关于仑伐替尼耐药机制及创新性应对策略的研究成果,为HCC患者进行仑伐替尼治疗提供新的参考。As an important first-line drug for advanced hepatocellular carcinoma(HCC),lenvatinib shows non-inferior therapeutic effects to sorafenib as well as better performance in certain aspects.However,lenvatinib resistance emerged eventually as most other anticancer drugs.Epidermal growth factor receptor(EGFR)bypass activation,the overexpression of fibroblast growth factor receptor 1(FGFR1)and the appearance of cancer stem cells in HCC are the causes of lenvatinib resistance.Lenvatinib combined with immune checkpoint inhibitors(ICIs)has been proven to have good efficacy in clinical trials.This review summarizes the new research findings on the mechanism of lenvatinib resistance and new strategies for improving the efficacy of lenvatinib in recent years,which could be helpful for treatment of HCC patients with lenvatinib.

关 键 词：肝细胞癌 仑伐替尼 耐药机制 治疗策略 

分 类 号：R735.7[医药卫生—肿瘤]