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

Ítalo Faria do Valle, Thomas Grinda, Lorenzo Antonuzzo, Barbara Pistilli

2025npj Breast Cancer19 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

MedicineBreast cancerCancer researchConjugateAcquired resistanceLinkerCancerDrug resistanceIdentification (biology)Computational biologyIntracellularBioinformaticsPharmacologyImmunotherapyAdeptBreast tumorCancer treatmentMonoclonal antibodyTrastuzumabSelection (genetic algorithm)Human breastCancer therapyCancer cellPayload (computing)HER2/EGFR in Cancer ResearchMonoclonal and Polyclonal Antibodies ResearchEstrogen and related hormone effects
Antibody–drug conjugates in breast cancer: mechanisms of resistance and future therapeutic perspectives | Litcius