抗体缀合药物（Antibody-Drug Conjugate）是近年来发展迅速的癌症治疗方法之一，已对乳腺癌显示出强大的活性。目前，已有2种抗体缀合药物被批准用于治疗HER2阳性乳腺癌、1种抗体缀合药物被批准用于治疗三阴性乳腺癌，多种研究性抗体缀合药物正在进行临床试验。不过，耐药问题已被临床注意，尤其恩美曲妥珠单抗。抗体缀合药物耐药机制可归纳为4类：抗体所致耐药、药物转运障碍、溶酶体功能破坏、有效载荷相关耐药。为了克服或预防抗体缀合药物耐药，正在研究创新的开发策略和联合治疗方案。
2022年11月10日，中国抗癌协会《癌症通讯》在线发表复旦大学附属肿瘤医院陈雨霏、邵志敏、余科达（通讯作者）、中国医科大学附属第一医院徐莹莹等学者长篇综述，对抗体缀合药物的研发背景、三大结构、作用机制、HER2和非HER2乳腺癌疗效、耐药机制及其解决方案进行了系统回顾，全文长达41页，参考文献多达180篇。
Cancer Commun (Lond). 2022 Nov 10. IF: 15.283
Resistance to antibody-drug conjugates in breast cancer: mechanisms and solutions.
Chen YF, Xu YY, Shao ZM, Yu KD.
Fudan University Shanghai Cancer Center, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Antibody-drug conjugates (ADCs) are a rapidly developing therapeutic approach in cancer treatment that has shown remarkable activity in breast cancer. Currently, there are two ADCs approved for the treatment of human epidermal growth factor receptor 2-positive breast cancer, one for triple-negative breast cancer, and multiple investigational ADCs in clinical trials. However, drug resistance has been noticed in clinical use, especially in trastuzumab emtansine. Here, the mechanisms of ADC resistance are summarized into four categories: antibody-mediated resistance, impaired drug trafficking, disrupted lysosomal function, and payload-related resistance. To overcome or prevent resistance to ADCs, innovative development strategies and combination therapy options are being investigated. Analyzing predictive biomarkers for optimal therapy selection may also help to prevent drug resistance.
KEYWORDS: Antibody-drug conjugate; breast cancer; combination therapy; drug resistance; predictive biomarker
PMID: 36357174
DOI: 10.1002/cac2.12387
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