靶向紧密连接蛋白6的药物在癌症治疗中的研究进展

Advances of Claudin6-targeting drugs in cancer therapy

紧密连接蛋白6(Claudin6,CLDN6)是紧密连接蛋白(Claudins,CLDNs)家族的一员,在卵巢癌、睾丸癌、子宫颈内膜癌、肝癌和肺腺癌等多种癌症中特异性高表达,而在成人正常组织中几乎不表达。其能够激活多条通路参与肿瘤发生的多个过程,包括促进肿瘤生长、迁移和侵袭,且促进肿瘤化疗耐药。近年来,CLDN6作为癌症治疗的新靶点引起了研究人员的广泛关注,针对CLDN6靶点开发了多种类型的抗癌药物,包括抗体偶联药物(antibody-drug conjugate,ADC)、单克隆抗体、双特异性抗体和嵌合抗原受体T细胞免疫疗法(chimeric antigen receptor T-cell immunotherapy,CAR-T)。本文简要概述了CLDN6的蛋白结构、表达分布以及在肿瘤中的功能,并对其作为药靶开发的抗癌药物研发现状和研发思路进行了综述。

CLDN6 is a member of the CLDNs family that is specifically and highly expressed in cancers such as ovarian,testicular,endocervical,liver and lung adenocarcinoma,but hardly expressed in adult normal tissues.CLDN6 is able to activate multiple signaling pathways,which take part in the development and progression of cancer,including promoting tumor growth,migration and invasion,and promoting chemoresistance in cancer.In recent years,CLDN6 has received much attention as a novel target for cancer therapeutics.Many types of anticancer drugs targeting CLDN6 have been developed,including antibody-conjugated drugs(ADC),monoclonal antibodies,bispecific antibodies,and chimeric antigen receptor T-cell immunotherapy(CAR-T).This paper briefly summarizes the structure,expression and function of CLDN6 in tumors,and reviews the current status and ideas of developing targeted CLDN6 anticancer drugs.