Vascular Disrupting Agents (VDAs) in Anticancer Therapy
Vascular Disrupting Agents (VDAs) in Anticancer Therapy
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DOI：
10.2174/157488410791498815
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发表时间：
2010-01-01
影响因子：
3.2
通讯作者：
Voest, Emile E.
中科院分区：
文献类型：
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作者：
Daenen, Laura G. M.;Roodhart, Jeanine M. L.;Voest, Emile E.
血管阻断剂（VDA）是一类靶向肿瘤血液供应的新型药物。VDA在概念和操作上与目前使用的抗血管生成剂不同，它对已建立但异常的肿瘤血管系统具有高度特异性。给药后，诱导肿瘤内皮细胞微管细胞骨架的快速变化，导致一系列事件，最终导致血流停滞和血管塌陷。随后，肿瘤核心的细胞坏死并死亡。然而，肿瘤再增殖发生在肿瘤边缘上的存活肿瘤组织的边缘，刺激了对设计用于干扰从存活边缘再生长的适当组合策略的研究。这些组合包括化疗、放疗和抗血管生成药物。近年来，对VDA治疗反应的分子和细胞机制的理解有了很大的提高。已经设计了多种药物组合，并在临床前模型中进行了测试，其中一些已经显示出令人鼓舞的结果。目前正在进行的一些临床试验（包括随机III期试验）中对临床获益进行调查。
Vascular disrupting agents (VDAs) represent a novel class of drugs targeting the tumor's blood supply. Conceptually and operationally different from currently used antiangiogenic agents, VDAs have a high specificity for the established but abnormal tumor vasculature. Upon administration, rapid changes in the microtubule cytoskeleton of tumor endothelial cells are induced, resulting in a cascade of events ultimately leading to blood flow stasis and vascular collapse. Subsequently, the cells in the core of the tumor become necrotic and die. However, tumor repopulation occurs from a rim of viable tumor tissue on the edges of the tumor, stimulating the search for appropriate combination strategies designed to interfere with the regrowth from the viable rim. Such combinations include chemotherapy, irradiation, and antiangiogenic drugs. In recent years, understanding of the molecular and cellular mechanisms taking place in response to VDA therapy has improved substantially. Multiple drug combinations have been designed and tested in preclinical models, some of which have shown encouraging results. Clinical benefits are currently under investigation in a number of ongoing clinical trials, including randomized phase III trials.