Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Tissue Barriers Pub Date : 2022-01-02 Epub Date: 2021-09-05 DOI:10.1080/21688370.2021.1967080

Daisuke Kyuno, Akira Takasawa, Kumi Takasawa, Yusuke Ono, Tomoyuki Aoyama, Kazufumi Magara, Yuna Nakamori, Ichiro Takemasa, Makoto Osanai

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Abstract

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.

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作为癌症治疗靶点的 Claudin-18.2：基础研究和临床试验的累积发现。

克劳蛋白是紧密连接的主要成分，可维持细胞的极性和细胞间的粘附性。克劳丁在癌细胞中的动态变化作为一种治疗靶点引起了人们的关注。在癌变过程中，claudin 的表达通常会下调；然而，在几种类型的癌症中观察到了claudin-18.2 的过度表达。癌细胞中克劳丁-18.2表达的上调和错位被认为是一种治疗靶点。对Claudin-18.2的研究表明，它参与了致癌过程。针对claudin-18.2的单克隆抗体唑贝妥昔单抗（zolbetuximab）用于晚期癌症患者的临床试验取得了积极的结果，且很少出现严重的不良反应；因此，它有望成为一种新型、有效的疗法。在此，我们回顾了目前对 claudin-18.2 在癌症基础研究和临床应用中所起作用的认识。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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.60

自引率

6.50%

发文量

期刊介绍： Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.