Combretastatin A-4 phosphate -: Vascular disrupting agent, oncolytic, treatment of age-related macular degeneration
Combretastatin A-4 phosphate -: Vascular disrupting agent, oncolytic, treatment of age-related macular degeneration
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DOI：
10.1358/dof.2007.032.12.1158960
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发表时间：
2007-12-01
影响因子：
0.2
通讯作者：
Bolos, J.
中科院分区：
文献类型：
--
作者：
Patterson, Daniel M.;Rustin, Gordon J. S.;Bolos, J.
Combretastatin A-4 磷酸盐（CA4P，Zybrestat (TM)）是一种血管破坏剂 (VDA)，可与微管蛋白结合并选择性损害已建立的肿瘤血管系统。临床前研究表明，CA4P 会导致血管快速关闭，导致中心肿瘤坏死，尽管它会在外围留下一圈活细胞，这需要额外的抗肿瘤治疗来增强疗效。 I 期单药治疗试验表明该药物具有良好的耐受性，最常见的副作用是肿瘤疼痛和轻度短暂的心血管效应。各种 CA4P 组合的临床试验已经进行或正在进行，初步取得了有希望的结果。临床前工作表明 CA4P 也能有效破坏眼部新生血管形成，并且已为静脉注射建立了人体概念验证。近视黄斑变性患者的药物；一种外用制剂正在开发中，作为年龄相关性黄斑变性（AMD）的潜在治疗方法。
Combretastatin A-4 phosphate (CA4P, Zybrestat (TM)) is a vascular disrupting agent (VDA) that binds to tubulin and selectively damages established tumor vasculature. Preclinical studies have shown that CA4P causes rapid vascular shutdown, leading to central tumor necrosis, although it leaves a rim of viable cells at the periphery, which requires additional antineoplastic treatment to enhance efficacy. Phase I monotherapy trials have shown the agent to be well tolerated, with tumor pain and mild transient cardiovascular effects being the most common side effects. Clinical trials of various CA4P combinations have been conducted or are ongoing with initially promising results. Preclinical work has shown CA4P to also be effective in disrupting ocular neovascularization, and human proof of concept was established for i.v. drug in patients with myopic macular degeneration; a topical formulation is in development as a potential treatment for age-related macular degeneration (AMD).