Molecular characteristics, regulatory mechanisms, and targeted therapeutic strategies of Claudin18.2 in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a rising incidence and a poor five-year survival rate. Current therapeutic strategies provide only limited survival benefit, underscoring the urgent need for novel therapeutic targets. The tight junction protein Claudin18.2 (CLDN18.2) is highly expressed in PDAC, presenting on tumor cell surfaces as a promising tumor-associated antigen with restricted expression in normal tissues. This review highlights the molecular characteristics, regulatory mechanisms, and targeted therapeutic developments of CLDN18.2 in PDAC, discussing the clinical progress and limitations of monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), chimeric antigen receptor T-cell therapy (CAR-T cell therapy), and antibody-drug conjugates (ADCs), as well as future prospects for combination strategies and next-generation agents.