Antibody–drug conjugates (ADCs) are emerging as a promising targeted treatment for pancreatic ductal adenocarcinoma (PDAC), one of the deadliest cancers with a five-year survival rate of about 10%. PDAC is difficult to treat because tumors are surrounded by dense fibrotic tissue that blocks drug delivery. The disease is also highly diverse at the molecular level and often evades the immune system, making many standard treatments less effective.
ADCs combine a monoclonal antibody that targets proteins on cancer cells with a powerful chemotherapy drug. Once the ADC binds to the tumor cell, it is internalized and releases the drug inside the cell to destroy it. Newer ADCs can also affect nearby tumor cells through a “bystander effect,” allowing the therapy to damage cancer cells even if they do not carry the specific target.
Researchers are investigating several promising ADC targets in pancreatic cancer, including uPAR, CLDN18.2, TROP2, mesothelin, and Nectin-4. Early studies have shown encouraging results, though side effects remain a concern. Future research is focusing on improving tumor penetration, developing ADCs that activate only within tumors, combining them with other therapies, and using artificial intelligence to design more personalized treatments.