Research Progress of CLDN18.2 in Gastric Cancer

Gastric cancer, as a globally prevalent malignancy with poor prognosis, exhibits limited efficacy to conventional therapies in advanced stages, necessitating novel therapeutic targets and strategies. CLDN18.2, a member of the Claudin protein family, is predominantly expressed in gastric mucosal epithelial cells under normal conditions, but is aberrantly overexpressed in malignancies such as gastric cancer. Its expression is closely associated with tumor invasion, metastasis, and poor prognosis, making it a highly promising therapeutic target. This paper elucidates the protein structure and biological functions of CLDN18.2, as well as its expression characteristics in gastric cancer. It systematically reviews clinical trial progress of various CLDN18.2-targeted agents, including monoclonal antibodies such as zolbetuximab, antibody-drug conjugates (ADCs) such as CMG901 and LM-302, bispecific antibodies such as Q-1802 and AMG910, and CAR-T cell therapies such as CT041. The efficacy and safety data of these agents in existing studies are analyzed. Furthermore, challenges in current research, including drug resistance, management of adverse effects, and precise patient selection, are discussed. Finally, future directions for optimizing drug design and exploring combination therapy strategies are proposed, providing a reference for the development of CLDN18.2-targeted therapies and the treatment of gastric cancer.