Next-generation drug conjugates for breast cancer: Clinical prospects and mechanism-based strategies to overcome resistance.

Antibody-drug conjugates (ADCs) have revolutionized breast cancer (BC) therapy, yet their efficacy is limited by resistance. With advances in ADC technology, broader paradigms of next-generation drug conjugates have emerged. For BC treatment, emerging drug conjugates under current clinical trials include degrader-antibody conjugates, antibody-oligonucleotide conjugates, immune-stimulating antibody conjugates, small molecule-drug conjugates, and peptide-drug conjugates. These agents exhibit significant potential in the treatment of BC and in bypassing ADC common resistance pathways through novel molecular mechanisms or delivery pathways. In this review, we elucidate the structures and mechanisms of these emerging drug conjugates, summarize their latest research progress, and analyze their potential to overcome ADC resistance, aiming to contribute to the development of drug conjugates in the future.