Antibody-drug conjugates (ADCs) represent a novel and promising approach in targeted therapy, uniting the specificity of antibodies that recognize specific antigens with payloads, all connected by the stable linker. These conjugates combine the best targeted and cytotoxic therapies, offering the killing effect of precisely targeting specific antigens and the potent cell-killing power of small molecule drugs. The targeted approach minimizes the off-target toxicities associated with the payloads and broadens the therapeutic window, enhancing the efficacy and safety profile of cancer treatments. Within precision oncology, ADCs have garnered significant attention as a cutting-edge research area and have been approved to treat a range of malignant tumors. Correspondingly, the issue of resistance to ADCs has gradually come to the fore. Any dysfunction in the steps leading to the ADCs' action within tumor cells can lead to the development of resistance. A deeper understanding of resistance mechanisms may be crucial for developing novel ADCs and exploring combination therapy strategies, which could further enhance the clinical efficacy of ADCs in cancer treatment. This review outlines the brief historical development and mechanism of ADCs and discusses the impact of their key components on the activity of ADCs. Furthermore, it provides a detailed account of the application of ADCs with various target antigens in cancer therapy, the categorization of potential resistance mechanisms, and the current state of combination therapies. Looking forward, breakthroughs in overcoming technical barriers, selecting differentiated target antigens, and enhancing resistance management and combination therapy strategies will broaden the therapeutic indications for ADCs. These progresses are anticipated to advance cancer treatment and yield benefits for patients.

中文翻译：

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聚焦抗体-药物偶联物中的理想靶抗原和耐药性：竞争进步策略


抗体药物偶联物 (ADC) 代表了靶向治疗中一种新颖且有前途的方法，它将识别特定抗原的抗体的特异性与有效负载结合在一起，所有这些都通过稳定的接头连接。这些缀合物结合了最佳的靶向和细胞毒性疗法，提供精确靶向特定抗原的杀伤作用和小分子药物的强大细胞杀伤能力。这种靶向方法最大限度地减少了与有效负载相关的脱靶毒性，并拓宽了治疗窗口，提高了癌症治疗的功效和安全性。在精准肿瘤学领域，ADC 作为前沿研究领域受到了广泛关注，并已被批准用于治疗一系列恶性肿瘤。相应地，ADC的抵制问题也逐渐凸显出来。导致 ADC 在肿瘤细胞内发挥作用的步骤中的任何功能障碍都可能导致耐药性的产生。更深入地了解耐药机制可能对于开发新型 ADC 和探索联合治疗策略至关重要，这可以进一步提高 ADC 在癌症治疗中的临床疗效。本综述概述了 ADC 的简要历史发展和机制，并讨论了其关键组成部分对 ADC 活动的影响。此外，它还详细介绍了具有各种靶抗原的 ADC 在癌症治疗中的应用、潜在耐药机制的分类以及联合治疗的现状。展望未来，克服技术障碍、选择差异化靶抗原、加强耐药管理和联合治疗策略等方面的突破将拓宽ADC的治疗适应症。 预计这些进展将促进癌症治疗并为患者带来益处。