A new perspective on antiangiogenic antibody drug resistance: Biomarkers, mechanisms, and strategies in malignancies

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-09-08 DOI:10.1002/ddr.22257
Chen Zhao, Yuan Zeng, Nannan Kang, Yu Liu
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Abstract

Drug resistance of malignant tumor leads to disease progression be the bottleneck in clinical treatment. Antiangiogenic therapy, which aims to “starve” the tumor by inhibiting angiogenesis, is one of the key strategies in clinical oncology treatments. Recently, dozens of investigational antibody drugs and biosimilars targeting angiogenesis have obtained regulatory approval for the treatment of various malignancies. Moreover, a new generation of bispecific antibodies based on the principle of antiangiogenesis are being advanced for clinical trial to overcome antiangiogenic resistance in tumor treatment or enhance the efficacy of monotherapy. Tumors often develop resistance to antiangiogenesis therapy, presenting as refractory and sometimes even resistant to new therapies, for which there are currently no effective management strategies. Thus, a detailed understanding of the mechanisms mediating resistance to antiangiogenesis antibodies is crucial for improving drug effectiveness and achieving a durable response to antiangiogenic therapy. In this review, we provide a novel perspective on the tumor microenvironment, including antibody structure, tumor stroma, and changes within tumor cells, to analyze the multifactorial reasons underlying resistance to antiangiogenesis antibodies. The review also enumerates biomarkers that indicate resistance and potential strategies for monitoring resistance. Furthermore, based on recent clinical and preclinical studies, we summarize potential strategies and translational clinical trials aimed at overcoming resistance to antiangiogenesis antibodies. This review provides a valuable reference for researchers and clinical practitioners involved in the development of new drugs or therapeutic strategies to overcome antiangiogenesis antibodies resistance.

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抗血管生成抗体耐药性的新视角:恶性肿瘤的生物标记物、机制和策略。
恶性肿瘤的耐药性导致疾病进展是临床治疗的瓶颈。抗血管生成治疗旨在通过抑制血管生成来 "饿死 "肿瘤,是临床肿瘤治疗的关键策略之一。最近,数十种针对血管生成的在研抗体药物和生物仿制药获得了监管部门的批准,用于治疗各种恶性肿瘤。此外,基于抗血管生成原理的新一代双特异性抗体也正在推进临床试验,以克服肿瘤治疗中的抗血管生成耐药性或提高单药治疗的疗效。肿瘤常常对抗血管生成治疗产生抗药性,表现为难治性,有时甚至对新疗法产生耐药性,目前尚无有效的治疗策略。因此,详细了解抗血管生成抗体的耐药机制对于提高药物疗效和实现抗血管生成治疗的持久应答至关重要。在这篇综述中,我们从抗体结构、肿瘤基质和肿瘤细胞内部变化等肿瘤微环境的新视角,分析了抗血管生成抗体耐药的多因素原因。综述还列举了表明抗药性的生物标志物和潜在的抗药性监测策略。此外,基于最近的临床和临床前研究,我们总结了旨在克服抗血管生成抗体耐药性的潜在策略和转化临床试验。这篇综述为参与开发克服抗血管生成抗体耐药性的新药或治疗策略的研究人员和临床工作者提供了宝贵的参考。
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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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