Advances of Peptide-Drug Conjugates in the Treatment of Digestive System Tumors

Digestive system tumors, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer, represent one of the most prevalent and lethal malignancy groups worldwide, with high incidence and mortality rates. Despite the continuous development of chemotherapy in cancer treatment, this traditional therapy generally suffers from insufficient tumor specificity, drug resistance and limited efficacy. Precise targeting strategies such as antibody-drug conjugates (ADCs) and peptide-drug conjugates (PDCs) combine cell-targeting delivery with potent antitumor activity and have demonstrated therapeutic potential in digestive system tumors. Compared with ADCs, PDCs offer advantages such as lower molecular weight, improved tumor penetration and reduced immunogenicity risk. Preclinical studies suggest that PDCs can enhance tumor-specific drug accumulation and reduce damage to normal tissues, which may compensate for the shortcomings of traditional chemotherapy. In this review, we systematically outline recent progress in PDC research for digestive system tumors, focusing on target selection and PDC design strategies. Representative PDCs targeting integrins, GPC3, EGFR, HER2, transferrin receptor, and VEGFR in digestive system tumors are highlighted. Based on the preclinical findings and early clinical results, we provide insights on future directions for PDC treatment in digestive system tumors.