Research advances in targeting claudin 18.2 in pancreatic ductal adenocarcinoma treatment

Claudin 18.2 (CLDN18.2) is a tight junction protein expressed only by gastric mucosal epithelial cells with known functions involving the regulation of cell barriers, polarity, and ion permeability. Research in cancers of the digestive system has shown that CLDN18.2 is often ectopically activated and highly expressed in gastric/gastroesophageal junction adenocarcinoma, and pancreatic cancer, identifying CLDN18.2 as a potential therapeutic target. Immunotherapy strategies targeting CLDN18.2 include monoclonal antibodies, chimeric antigen receptor T cells, diclonal antibodies, and antibody conjugates, and such therapies have shown promising efficacy in gastric cancer. Zolbetuximab, a monoclonal antibody, has also shown promise in the treatment of pancreatic ductal adenocarcinoma (PDAC). This review summarizes and discusses major advances related to the function and targeting of CLDN18.2 in PDAC. By understanding the structure, function, and expression of CLDN18.2 in PDAC as well as the efficacy and mechanisms of treatment methods related to CLDN18.2, we hope to provide insights for the future development of treatment strategies for CLDN18.2-positive PDAC. However, current evidence on the clinical efficacy of targeting CLDN18.2 in PDAC remains preliminary and fragmented, derived mostly from small studies or gastric cancer extrapolation. Much more research is needed before clinical application of CLDN18.2-directed strategies.