Claudins and Gastric Cancer: An Overview

Simple Summary Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer deaths worldwide, with a high frequency of recurrence and metastasis, and a poor prognosis. This review presents novel biological and clinical significance of claudin (CLDN) expression in GC, especially CLDN18, and clinical trials centered around CLDN18.2. It also presents new findings for other CLDNs. Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial-mesenchymal transition (EMT) and cell-cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell-cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18-ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. Herein, we review the literature on CLDNs, focusing on CLDN18 in GC.

Automated summary

This review highlights the biological and clinical significance of claudin (CLDN) expression in gastric cancer (GC), with a focus on CLDN18.2 and clinical trials centered around it. Abnormal expression of CLDNs, particularly CLDN18, is observed in GC. CLDNs are potential targets for antibody drugs in GC treatment.