CLDN18-ARHGAP fusion

Additionally, there have been preclinical advancements in exploiting unique therapeutic vulnerabilities in several models of DGC through targeting of the focal adhesion kinase (FAK) and Hippo pathways. These preclinical and clinical advancements represent a promising future for the treatment of DGC.

These results indicate that the CLDN18-ARHGAP26 fusion is a gain-of-function DGC oncogene that leads to activation of RHOA and activation of FAK and YAP signalling. These results argue for further evaluation of emerging FAK and YAP-TEAD inhibitors for these deadly cancers.

Also, we revealed the role of CLDN18-ARHGAP fusion gene in promoting a suppressive TIME by facilitating the metabolism and proliferation of Tregs, which could be reversed by PI3Ki. Collectively, we demonstrated that CLDN18-ARHGAP is a potential target for immunotherapies in gastric cancer.

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.