Xing Ping, Yang Chenghui, Hu Hanwen, Qian Tianyi, Xie Bojian, Huang Jian, Wang Zhen
Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
Cancer Drug Resist. 2025 Jun 17;8:29. doi: 10.20517/cdr.2025.26. eCollection 2025.
Antibody-drug conjugates (ADCs), inspired by Paul Ehrlich's "magic bullet" concept to target cancer cells with cytotoxic drugs while sparing healthy cells, represent a transformative approach in breast cancer therapy. From early agents (e.g., gemtuzumab ozogamicin) to second-generation trastuzumab emtansine (T-DM1) and third-generation trastuzumab deruxtecan (T-DXd)/disitamab vedotin (RC48), ADCs have demonstrated significant clinical benefits, including improved progression-free survival (PFS) and overall survival (OS) in breast cancer, with several approved for clinical use. Ongoing preclinical and clinical studies are rigorously exploring ADC combinations with molecular targeted agents, chemotherapy, and immunotherapy. However, and acquired resistance remains a critical barrier to maximizing therapeutic efficacy. This review summarizes ADC mechanisms and clinical outcomes in breast cancer, explores resistance mechanisms, and dissects the biological rationale for combination strategies, aiming to identify novel payloads that enhance patient outcomes.
抗体药物偶联物（ADCs）的灵感来源于保罗·埃尔利希的“神奇子弹”概念，即利用细胞毒性药物靶向癌细胞，同时保护健康细胞，是乳腺癌治疗中的一种变革性方法。从早期药物（如吉妥珠单抗奥唑米星）到第二代曲妥珠单抗恩美曲妥珠单抗（T-DM1）和第三代曲妥珠单抗德曲妥珠单抗（T-DXd）/迪西他单抗维泊妥珠单抗（RC48），ADCs已显示出显著的临床益处，包括改善乳腺癌患者的无进展生存期（PFS）和总生存期（OS），已有数种获批用于临床。正在进行的临床前和临床研究正在严格探索ADCs与分子靶向药物、化疗和免疫疗法的联合应用。然而，耐药性和获得性耐药仍然是最大化治疗效果的关键障碍。本综述总结了ADCs在乳腺癌中的作用机制和临床结果，探讨了耐药机制，并剖析了联合策略的生物学原理，旨在识别可改善患者预后的新型有效载荷。
