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

Tissue Barriers. 2022 Jan 2;10(1):1967080. doi: 10.1080/21688370.2021.1967080. Epub 2021 Sep 5.

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.

Keywords: Tight junction; cancer; claudin-18.2; zolbetuximab.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinogenesis / metabolism
  • Cell Adhesion Molecules / metabolism
  • Claudins* / metabolism
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Tight Junctions / metabolism

Substances

  • Cell Adhesion Molecules
  • Claudins

Grants and funding

This work was supported by JSPS KAKENHI under the grant number [JP19K24018]