Abstract
Claudin 18.2 (CLDN18.2) is a tight-junction protein. CLDN18.2-targeting strategy has cut a striking figure in CLDN18.2 positive patients with advanced gastric cancer. Zolbetuximab, the CLDN18.2 antibody, obtained a better clinical benefit in patients compared with the controlled. In phase II trials, combination treatment of epirubicin, oxaliplatin and capecitabine (EOX) + zolbetuximab achieved the optimal effects of overall survival which extended to 13.2 months with tolerable safety events, indicating its greater potential playing the second promising target in gastric cancer. This review will reveal the definitive clinical benefit CLDN18.2-targeting therapies have achieved and update the highlighting development (like chimeric antigen receptor T-cell immunotherapy) to CLDN18.2 positive patients. We then focus on 10 questions arisen from recent progress and anticipate to provide a future perspective for novel cancer treatment.