Advances and challenges of chimeric antigen receptor T cell therapy in digestive system malignancies

Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized the treatment of hematologic malignancies, but its success in solid tumors, particularly those of the digestive system, remains limited. Tumors of the gastrointestinal system, including gastric, colorectal, esophageal, hepatic, and pancreatic malignancies, represent a significant global health burden with high morbidity and mortality. Recent advances in antigen selection, chimeric antigen receptor design, delivery techniques, and combinatorial approaches have sparked renewed interest in CAR-T immunotherapy for these cancers. This article discusses recent progress in CAR-T development across the major digestive system tumors, outlines tumor-specific targets and clinical trials, highlights prevailing challenges and potential solutions, and proposes strategic directions for the next generation of CAR-T therapies in solid tumors.