Emerging targets in gastric and pancreatic cancer: Focus on claudin 18.2
Alireza Tojjari, Yassine Alami Idrissi, Anwaar Saeed
Abstract
Recently, the molecular landscape of gastric and pancreatic cancers has advanced with Claudin 18.2 (CLDN18.2) emerging as a promising therapeutic target. Claudin 18.2, a tight junction protein, is selectively expressed in cancer cells and minimally in normal tissues, making it an attractive candidate for targeted therapy. Therapies like monoclonal antibodies (e.g., zolbetuximab), bispecific antibodies, and antibody-drug conjugates have shown significant potential in improving clinical outcomes. Early-phase clinical trials demonstrate robust antitumor activity, particularly in combination with chemotherapy and immunotherapy regimens. However, challenges such as patient selection, resistance mechanisms, and toxicity management remain critical. This review highlights the therapeutic landscape, clinical advancements, and future directions of targeting Claudin 18.2 in gastric and pancreatic cancer treatment. • Claudin 18.2 is a selective target in gastric and pancreatic cancer therapy. • Zolbetuximab shows promise by improving survival in gastric cancer. • New antibody-drug conjugates target Claudin 18.2-positive tumors. • Claudin 18.2 CAR T-cell therapy demonstrates potent antitumor activity. • Combination therapies with Claudin 18.2 enhance treatment efficacy.