Targeting Claudin18.2 for cancer theranostics: From molecular imaging to precision therapy

Claudin18.2 (CLDN18.2), a specific tight junction protein isoform, is minimally expressed in normal gastric mucosa but aberrantly overexpressed in various cancers. It plays a key role in regulating tumor cell differentiation, proliferation, and migration, making it an attractive therapeutic target, especially in gastric cancer. Moreover, molecular imaging techniques such as immuno-positron emission tomography, immuno-single photon emission computed tomography, and near-infrared fluorescence imaging enable non-invasive evaluation of CLDN18.2 expression, improving diagnosis and guiding personalized treatment. This review summarizes recent advances in CLDN18.2-targeted therapies and molecular imaging for cancer management. We outline the biomarker's biological functions and signaling pathways across cancers, highlighting the development of precision therapeutics. We also discuss applications and limitations of CLDN18.2-targeted theranostics in digestive malignancies and address clinical translation challenges and future directions.