Poniewierska-Baran Agata, Plewa Paulina, Żabicka Zuzanna, Pawlik Andrzej
Institute of Biology, University of Szczecin, Felczaka 3c, 71-412 Szczecin, Poland.
Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland.
Cells. 2025 Aug 19;14(16):1285. doi: 10.3390/cells14161285.
Claudin-18.2 (CLDN18.2) is an isoform of a tight junction protein and has emerged as a promising therapeutic target in gastric cancer (GC). CLDN18.2 is responsible for gastric homeostasis and protects epithelial cells from low pH conditions. Interestingly, CLDN18.2 expression is strictly restricted to the stomach, making it an ideal tumor marker. This narrative review presents the characterization and role of claudin 18.2 (CLDN18.2) as a promising biomarker in GC and a target for clinical therapies, more specifically CLDN18.2-targeted drugs and therapies including mABs (e.g., Zolbetuximab, Osemitamab, ZL-1211), bsAB, and CAR-T cell-based immunotherapies. We also summarize numerous ongoing worldwide clinical trials that are evaluating CLDN18.2 as a target for GC treatment. What seems to be crucial is that preclinical and clinical data indicate their high efficacy and safety.
紧密连接蛋白 Claudin-18.2（CLDN18.2）是紧密连接蛋白的一种异构体，已成为胃癌（GC）中一个有前景的治疗靶点。CLDN18.2 负责维持胃部内环境稳定，并保护上皮细胞免受低 pH 环境影响。有趣的是，CLDN18.2 的表达严格局限于胃部，使其成为一种理想的肿瘤标志物。本叙述性综述介绍了 Claudin 18.2（CLDN18.2）作为 GC 中有前景的生物标志物以及临床治疗靶点的特征和作用，更具体地说，包括 CLDN18.2 靶向药物和疗法，如单克隆抗体（如 Zolbetuximab、Osemitamab、ZL-1211）、双特异性抗体和基于嵌合抗原受体 T 细胞（CAR-T）的免疫疗法。我们还总结了全球范围内众多正在进行的将 CLDN18.2 作为 GC 治疗靶点的临床试验。关键的是，临床前和临床数据表明它们具有高疗效和安全性。
