Li Sijia, Zhao Xinyu, Fu Kai, Zhu Shuangli, Pan Can, Yang Chuan, Wang Fang, To Kenneth K W, Fu Liwu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
School of Pharmacy, the Chinese University of Hong Kong, Hong Kong 999077, China.
Acta Pharm Sin B. 2025 Feb;15(2):737-756. doi: 10.1016/j.apsb.2024.12.036. Epub 2024 Dec 31.
Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.
抗体药物偶联物（ADCs）是由单克隆抗体和通过连接子共价偶联的细胞毒性载荷组成的抗肿瘤药物。目前，全球已有15种ADCs获得临床批准。超过100项不同阶段的临床试验正在进行，以研究新开发的ADCs。ADCs是肿瘤药物开发中增长最快的靶向抗肿瘤药物类别之一。它利用抗体对肿瘤特异性抗原的特异性靶向作用，将细胞毒性化疗药物精确递送至肿瘤细胞，从而产生有前景的抗肿瘤疗效和良好的不良反应谱。然而，耐药性的出现严重阻碍了ADCs的临床疗效。在本综述中，我们介绍了ADCs的结构和机制，描述了ADCs的发展，总结了关于ADCs耐药机制的最新研究，讨论了克服ADCs耐药的策略，并预测了ADCs治疗反应的生物标志物，旨在为未来ADCs的发展做出贡献。
