CLDN18.2蛋白在恶性肿瘤治疗中的研究进展

随着分子生物学研究的进展,靶向治疗已成为除手术、放疗、化疗之外恶性肿瘤治疗中的第四种有效手段。与传统化疗药物不同,分子靶向治疗药物具有特异性强、疗效明显、不良反应较小等优点。CLDN18.2蛋白是新发现的一种跨膜蛋白,具有高选择性特点,稳定地过表达于多种恶性肿瘤中,尤其是消化系统肿瘤及其转移瘤。近年来,其特异性抗体claudiximab(zolbetuximab/IMAB362)在最新的临床试验中取得了显著的成功,CLDN18.2蛋白有望成为某些特定恶性肿瘤靶向治疗的分子靶点。

CLDN18.2在胃癌中的研究进展

CLDN18.2是表达于正常胃黏膜的紧密连接蛋白,参与构成细胞间的紧密连接,影响细胞旁离子通透性。CLDN18.2在胃癌中阳性率可达40%左右,其表达特异性使其成为胃癌治疗的潜在靶点。靶向CLDN18.2的抗体药IMAB362联合化疗可显著延长CLDN18.2阳性胃癌患者生存,IMAB362有望进入胃癌一线治疗。然而由于检测抗体研发瓶颈,截止目前有关CLDN18.2研究有限,此外由于CLDN18.2临床试验处于初始阶段,目前研究结果尚不明了,关于CLDN18.2阳性胃癌的认识仍缺乏整体观。本文对CLDN18.2相关的既往研究及进展进行综述,以期整合CLDN18.2相关进展,为CLDN18.2阳性胃癌临床及转化研究提供参考,并为其未来发展方向提供可能的思路。

Future of targeted therapy for gastrointestinal cancer:Claudin 18.2

The treatment of gastrointestinal cancer has always been a crucial research area,and targeted therapy has been receiving increasing attention.At present,the effect of targeted therapy is unsatisfactory for gastric cancer.Thus,the discovery of new targets is crucial.Claudin 18.2(CLDN18.2),a member of the claudin family,belongs to the tight junction protein family that controls the flow of molecules between cell layers.CLDN18.2 expression has been discussed in many studies.In recent years,there have been many studies on targeted therapy with CLDN18.2-ideal monoclonal antibody 362.Furthermore,CLDN18.2-specific chimeric antigen receptor T therapy has been used for CLDN18.2-positive tumors,such as gastric and pancreatic cancers.Considerable research has been focused on CLDN18.2.CLDN18.2,a newly discovered marker for precise targeted therapy of gastric cancer,could offer new hope for the treatment of gastric cancer.