Department of Pathology, Sapporo Medical University, Sapporo, Japan.
Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan.
Tissue Barriers. 2022 Jan 2;10(1):1967080. doi: 10.1080/21688370.2021.1967080. Epub 2021 Sep 5.
Claudins are major components of tight junctions that maintain cell polarity and intercellular adhesion. The dynamics of claudins in cancer cells have attracted attention as a therapeutic target. During carcinogenesis, claudin expression is generally downregulated; however, overexpression of claudin-18.2 has been observed in several types of cancers. Upregulated and mislocalized claudin-18.2 expression in cancer cells has been suggested as a therapeutic target. Research on claudin-18.2 has revealed its involvement in carcinogenesis. Clinical trials using zolbetuximab, a monoclonal antibody targeting claudin-18.2, for patients with advanced cancer yielded positive results with few high-grade adverse events; thus, it is expected to be a novel and effective therapeutic. Here, we review current insights into the role that claudin-18.2 plays in basic cancer research and clinical applications. A better understanding of these roles will facilitate the development of new treatment strategies for cancer patients with poor prognoses.
紧密连接的主要成分是 Claudin，它维持着细胞极性和细胞间黏附。 Claudin 在癌细胞中的动态变化作为治疗靶点引起了关注。在癌变过程中，Claudin 的表达通常下调；然而，在几种类型的癌症中观察到 Claudin-18.2 的过表达。癌细胞中 Claudin-18.2 的上调和定位错误表达被认为是治疗靶点。对 Claudin-18.2 的研究揭示了其在致癌作用中的参与。使用针对 Claudin-18.2 的单克隆抗体 Zolbetuximab 对晚期癌症患者进行的临床试验取得了积极的结果，仅有少数高级别不良事件；因此，它有望成为一种新的有效治疗方法。在这里，我们综述了 Claudin-18.2 在基础癌症研究和临床应用中的作用的最新认识。更好地了解这些作用将有助于为预后不良的癌症患者开发新的治疗策略。
