靶向TROP-2抗体药物偶联物戈沙妥珠单抗在转移性三阴性乳腺癌治疗中的应用进展

Advances in the Application of Sacituzumab Govitecan, a TROP-2-Targeted Antibody-Drug Conjugate, in the Treatment of Metastatic Triple-Negative Breast Cancer

摘要

作为靶向滋养层细胞表面抗原2（trophoblast cell-surface antigen 2，TROP-2）的抗体药物偶联物（antibody-drug conjugate，ADC），戈沙妥珠单抗由靶向抗体、可水解连接子（carbonate linker，CL2A）和高效拓扑异构酶Ⅰ抑制剂7-乙基-10-羟基喜树碱（7-ethyl-10-hydroxycamptothecin，SN-38）组成。近年来，随着临床诊疗技术的持续发展，戈沙妥珠单抗在转移性三阴性乳腺癌（metastatic triple-negative breast cancer，mTNBC）的治疗方面取得了较大进展。III期ASCENT研究确立了戈沙妥珠单抗的后线治疗地位，ASCENT-03研究进一步证实了其一线治疗价值，多项全球真实世界研究亦验证了该药在复杂临床场景下应用的有效性与安全性，标志着ADC药物治疗模式已从传统实验室研究转向临床实践优化阶段。基于最新临床研究与真实世界数据，重点阐述戈沙妥珠单抗对mTNBC现有治疗瓶颈的突破及其对治疗格局的拓宽，同时，系统分析现阶段该药物在生物标志物检测、耐药机制及药物经济学等方面面临的核心挑战。

Abstract

As an antibody-drug conjugate (ADC) targeting trophoblast cell-surface antigen 2 (TROP-2), sacituzumab govitecan consists of a targeting antibody, a hydrolyzable carbonate linker (CL2A), and the potent topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN-38). In recent years, with the continuous development of clinical diagnosis and treatment technologies, considerable progress has been made in the treatment of metastatic triple-negative breast cancer (mTNBC) with sacituzumab govitecan. The phase III ASCENT trial has established its role in later-line treatment, and the ASCENT-03 trial has confirmed its first-line therapeutic value. In addition, multiple real-world studies worldwide have verified the efficacy and safety of sacituzumab govitecan in complex clinical settings, indicating that the ADC treatment paradigm has shifted from traditional laboratory-based research to clinical practice optimization. Based on the latest clinical research and real-world data, this review focuses on how sacituzumab govitecan overcomes the existing therapeutic limitations of mTNBC and expands its treatment landscape. It also systematically analyzes the core challenges currently facing this drug, including biomarker testing, resistance mechanisms, and pharmacoeconomics.

关键词

戈沙妥珠单抗 / 抗体药物偶联物 / 转移性三阴性乳腺癌 / 滋养层细胞表面抗原2

Key words

sacituzumab govitecan / antibody-drug conjugate / metastatic triple-negative breast cancer / trophoblast cell-surface antigen 2

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