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Claudins and Gastric Cancer: An Overview
Itaru Hashimoto1,2, Takashi Oshima1
1Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama 241-8515, Japan.
Abstract:
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.
Insights
Claudins (CLDNs), particularly CLDN18, are highly expressed in gastric cancer (GC) and are promising targets for new antibody therapies. Research focuses on CLDNs
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Advanced gastric cancer (GC) frequently recurs and metastasizes, necessitating novel therapeutic targets.
- Epithelial-mesenchymal transition (EMT), driven by loss of cell-cell adhesion, is crucial for cancer metastasis.
- Claudins (CLDNs), components of tight junctions, exhibit abnormal expression in various cancers, including GC.
Purpose of the Study:
- To review the literature on Claudins (CLDNs) in gastric cancer (GC).
- To highlight CLDN18 as a significant target for GC treatment.
- To discuss the potential of CLDNs as targets for novel antibody therapies in GC.
Main Methods:
- Literature review of studies on Claudins (CLDNs) in gastric cancer (GC).
- Analysis of The Cancer Genome Atlas (TCGA) data for GC molecular subtypes and gene fusions.
- Examination of clinical trial data for anti-CLDN18.2 antibody drugs in GC treatment.
Main Results:
- Abnormal expression of multiple CLDNs (CLDN1, 2, 3, 4, 6, 7, 10, 11, 14, 17, 18, 23) is reported in GC.
- CLDN18, specifically, is of significant interest, with a CLDN18-ARHGAP fusion identified in a GC subtype.
- An anti-CLDN18.2 antibody drug shows promising therapeutic potential for GC.
Conclusions:
- Claudins (CLDNs) are highly expressed in GC and play a role in tight junctions.
- CLDN18 is a particularly promising target for novel therapeutic strategies in GC.
- CLDNs are viable targets for the development of new antibody-based drugs for gastric cancer treatment.
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