Claudins and Gastric Cancer: An Overview.

Takashi Oshima,Itaru Hashimoto

doi:10.3390/cancers14020290

Takashi Oshima, Itaru Hashimoto

Open Access

https://doi.org/10.3390/cancers14020290

Copy DOI

Abstract

Simple SummaryGastric 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.

Highlights

Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer-related deaths worldwide, with a high incidence in East Asia [1]
These results showed that treatment with IMAB362 targeting CLDN18.2 for patients with GC is an effective and safe treatment
CLDN6 was identified as an overexpressed gene in GC tumors compared to adjacent normal tissues, and its high expression was positively correlated with decreased overall survival (OS) in patients with GC [51,52]

Summary

Introduction

Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer-related deaths worldwide, with a high incidence in East Asia [1]. The first step in cancer metastasis is local infiltration into the surrounding tumorrelated stroma and normal tissue. The first stage of EMT is the breakdown of contact between epithelial cells, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions, eventually resulting in the loss of cell polarity, cytoskeletal reorganization, and cells. Among these contacts, TJs comprise endogenous membrane proteins, such as claudin (CLDN) and occludin, and cytoplasmic proteins zonula occludens 1 (ZO1), ZO2, and ZO3, which are transmembrane proteins. The expression of CLDN has been reported in several types of cancer, including GC, and has recently attracted attention as a new therapeutic target [7]. We add new findings to literature on CLDNs, with a focus on CLDN18 in GC, and highlight its potential for research as well as the clinical application of CLDNs

General Information of CLDNs

CLDN18

Design

CLDN10

Findings

Conclusions