CLDN18.2, a stomach-specific tight junction protein, is normally low but becomes upregulated in multiple cancers, including gastric, pancreatic, colorectal, breast, and liver tumors. This dysregulation promotes tumor growth and spread, making it a promising biomarker and therapeutic target. Its expression is regulated by transcriptional, epigenetic, and signaling pathways, and it has context-dependent effects—mostly oncogenic, but occasionally tumor-suppressive.
Therapeutic advances targeting CLDN18.2 are rapidly expanding. Zolbetuximab, the first FDA-approved antibody, improves survival in HER2-negative, CLDN18.2-positive gastric cancers. Next-generation antibodies (Osemitamab, ASKB589), bispecific antibodies (Gresonitamab), antibody-drug conjugates (CMG901, SYSA1801), and CAR-T therapies (CT041) offer enhanced tumor targeting with limited toxicity.
Molecular imaging using ImmunoPET, ImmunoSPECT, and near-infrared fluorescence enables precise detection and intraoperative guidance. Together, CLDN18.2-targeted therapy and imaging form a theranostic strategy, integrating diagnosis and treatment to improve patient selection and outcomes in gastrointestinal and other solid tumors.