Abstract:

Claudin 18.2 (CLDN18.2), a transmembrane protein belonging to the Claudin family, primarily participates in forming tight junction structures between cells to maintain epithelial cell polarity and barrier function. While exhibiting low expression in normal healthy tissues, it is aberrantly overexpressed on the surface of tumor cells due to disrupted tight junctions and is closely associated with tumor proliferation, invasion, metastasis, and poor prognosis. In december 2024, zolbetuximab received approval from the National Medical Products Administration (NMPA) for use in combination with fluorouracil-based and platinum-containing chemotherapy regimens as first-line treatment for patients with CLDN18.2-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. This drug represents the world's first approved monoclonal antibody targeting CLDN18.2 and marks China's inaugural innovative therapy for this target. This article reviews the molecular structure and physicochemical properties, pharmacological mechanism and clinical research progress of zolbetuximab, and discusses its future application potential and development direction in the field of tumor therapy.

Key words: zolbetuximab, Claudin18.2, gastric or gastroesophageal junction adenocarcinoma