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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月29日

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  • Irene Valle,
  • Thomas Grinda,
  • Lorenzo Antonuzzo,
  • Barbara Pistilli

摘要

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.