Spotlight on ideal target antigens and resistance in antibody-drug conjugates: Strategies for competitive advancement

IF 15.8 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Mingxia Jiang , Qiao Li , Binghe Xu
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Abstract

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.

聚焦抗体药物共轭物中的理想靶抗原和抗药性:提高竞争力的策略
抗体-药物共轭物(ADCs)是靶向治疗中一种新型且前景广阔的方法,它将识别特定抗原的特异性抗体与有效载荷结合在一起,所有载荷都由稳定的连接体连接。这些共轭物结合了最佳的靶向疗法和细胞毒疗法,既有精确靶向特定抗原的杀伤效果,又有小分子药物强大的细胞杀伤力。这种靶向方法最大限度地减少了有效载荷的脱靶毒性,扩大了治疗窗口,提高了癌症治疗的有效性和安全性。在精准肿瘤学领域,ADC 作为一个前沿研究领域备受关注,已被批准用于治疗一系列恶性肿瘤。相应地,ADCs 的耐药性问题也逐渐凸显出来。ADCs在肿瘤细胞内发挥作用的任何步骤出现功能障碍,都可能导致耐药性的产生。深入了解耐药机制可能对开发新型 ADC 和探索联合治疗策略至关重要,这将进一步提高 ADC 在癌症治疗中的临床疗效。本综述概述了 ADCs 的简要历史发展和机制,并讨论了其关键成分对 ADCs 活性的影响。此外,它还详细介绍了ADCs与各种靶抗原在癌症治疗中的应用、潜在耐药机制的分类以及联合疗法的现状。展望未来,在克服技术壁垒、选择差异化靶抗原、加强耐药性管理和联合治疗策略方面取得的突破将拓宽 ADCs 的治疗适应症。预计这些进展将推动癌症治疗,为患者带来益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Drug Resistance Updates
Drug Resistance Updates 医学-药学
CiteScore
26.20
自引率
11.90%
发文量
32
审稿时长
29 days
期刊介绍: Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. *Expert reviews in clinical and basic drug resistance research in oncology and infectious disease *Describes emerging technologies and therapies, particularly those that overcome drug resistance *Emphasises common themes in microbial and cancer research
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