摘要
肝细胞癌(hepatocellular carcinoma,HCC)是中国发病率和死亡率较高的恶性肿瘤之一,大多数患者确诊时已进入晚期。酪氨酸激酶抑制剂索拉非尼和仑伐替尼是中晚期HCC的一线治疗药物,但疗效十分有限。近年来,针对程序性死亡受体-1(programmed cell death protein-1,PD-1)、程序性死亡配体-1(programmed cell death ligand-1,PD-L1)以及细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)等免疫检查点抑制剂(immune checkpoint inhibitor,ICI)的单抗治疗在多种实体瘤的临床试验中取得了令人瞩目的成效。纳武单抗、帕博利珠单抗和卡瑞利珠单抗等ICI也先后获批用于晚期HCC的治疗。基于ICI的联合治疗方案,包括ICI联合血管内皮生长因子抑制剂、ICI联合酪氨酸激酶抑制剂、2种ICI的联合应用以及ICI联合HCC局部治疗等均已进入临床试验阶段,尤其是阿特珠单抗与贝伐珠单抗的联合治疗的效果优于索拉非尼,能显著延长患者的总生存期,目前已获批成为晚期HCC的一线治疗方案。本文就ICI在晚期HCC治疗中的效果及机制进行总结,重点介绍ICI联合治疗方案所取得的突破性进展,并对其瓶颈问题和应用前景进行了讨论和展望。
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in China,and most cases are diagnosed at advanced stage.The multikinase inhibitors sorafenib and lenvatinib are currently firstline therapies for advanced HCC,but the response rates are limited and the drug resistances are increasing.In recent years,the immune checkpoint inhibitors(ICIs),including anti-programmed cell death protein-1(PD-1)/programmed cell death ligand-1(PD-L1)and anticytotoxic T lymphocyte-associated antigen-4(CTLA-4)monoclonal antibodies,have demonstrated promising efficacy in cancer clinical trials.Up to now,ICIs such as nivolumab,pembrolizumab and carrelizumab have been approved for the therapy of advanced HCC.Furthermore,the ICIs combination treatments,including ICIs combined with vascular endothelial growth factor inhibitors,tyrosine kinase inhibitors,other ICIs,or topical remedy,are being tested in clinical trials.In particular,the combination therapy of atezolizumab and bevacizumab is significantly superior to sorafenib in prolonging the overall survival,so it is granted as the first-line therapy for advanced HCC.This paper reviews the underlying mechanism of ICIs therapy for advanced HCC and the results of clinical trials and discuss the drawbacks and the potential of ICIs.
作者
李鑫
高见
屠红
LI Xin;GAO Jian;TU Hong(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
2021年第12期866-875,共10页
Tumor
基金
国家自然科学基金资助项目(81872505
81572312)
癌基因与相关基因国家重点实验室自主资助项目(ZZ 94-21-09)。
关键词
肝细胞癌
免疫检查点抑制剂
联合治疗
Hepatocellular carcinoma
Immune checkpoint inhibitor
Combination therapy