Antibody–drug conjugates in breast cancer: mechanisms of resistance and future therapeutic perspectives

Although antibody–drug conjugates (ADCs) revolutionized cancer treatment, especially in breast cancer, resistance remains a major challenge. It may involve target expression and distribution, linker stability, ADC intratumor penetration and intracellular internalization, payload activity but also interaction with the tumor microenvironment. Strategies to overcome resistance under investigation include combination therapies, novel payloads, and next-generation ADC designs. The identification of predictive biomarkers may also help guide treatment selection and prevent resistance.