Innovative CAR-T approaches targeting Claudin 18.2 to counteract drug resistance in gastric cancer

Claudins, integral components of tight junctions, have recently emerged as key modulators of drug resistance in gastric cancer. Claudin18.2 is aberrantly expressed in a subset of gastric tumors, where it disrupts epithelial integrity and promotes tumor progression and therapeutic failure. By orchestrating cell death and survival processes, including apoptosis, autophagy, and epithelial-mesenchymal transition pathways, Claudin 18.2 enhances multidrug resistance and is associated with adverse clinical outcomes. Furthermore, its crosstalk with efflux transporters and pro-survival signaling pathways further reinforces chemoresistance to platinum-based drugs and fluoropyrimidines. Growing evidence identifies Claudin18.2 as both a biomarker of aggressive disease and an attractive therapeutic target. Monoclonal antibodies and antibody-drug conjugate directed against Claudin18.2 are currently being evaluated in clinical trials, showing encouraging antitumor activity.