Anti-VEGF/VEGFR therapy for cancer: reassessing the target.
Anti-VEGF/VEGFR therapy for cancer: reassessing the target.
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DOI：
10.1158/0008-5472.can-11-3406
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发表时间：
2012-04-15
期刊：
影响因子：
11.2
通讯作者：
Dvorak HF
中科院分区：
文献类型：
--
作者：
Sitohy B;Nagy JA;Dvorak HF
Judah Folkman认识到新血管形成对肿瘤生长很重要，并提出抗血管生成作为癌症治疗的新方法。血管通透性因子/血管内皮生长因子（VEGF-A）作为主要肿瘤血管生成因子的发现促使许多靶向其或其受体的药物的开发。这些药物通常成功地阻止肿瘤血管生成和消退快速生长的小鼠肿瘤。然而，在人类癌症中的结果却不那么令人印象深刻。许多原因已经提供了缺乏更大的成功，我们在这里提请注意的异质性的肿瘤血管作为一个重要的问题。人类和小鼠肿瘤由至少六种明确定义的血管类型提供，这些血管类型由血管生成和动静脉生成产生。所有六种类型都可以通过表达VEGF-A164的腺病毒载体在小鼠组织中产生。一旦形成，六种类型中的四种失去了它们的VEGF-A依赖性，因此它们对抗VEGF/VEGFR治疗的反应性。如果针对血管系统的治疗对人类癌症有更大的影响，则需要在这些耐药肿瘤血管上鉴定VEGF及其受体以外的靶点。
Judah Folkman recognized that new blood vessel formation is important for tumor growth and proposed anti-angiogenesis as a novel approach to cancer therapy. Discovery of vascular permeability factor/vascular endothelial growth factor (VEGF-A) as the primary tumor angiogenesis factor prompted the development of a number of drugs that targeted it or its receptors. These agents have often been successful in halting tumor angiogenesis and in regressing rapidly growing mouse tumors. However, results in human cancer have been less impressive. A number of reasons have been offered for the lack of greater success, and we here call attention to the heterogeneity of the tumor vasculature as an important issue. Human and mouse tumors are supplied by at least six well-defined blood vessel types that arise by both angiogenesis and arterio-venogenesis. All six types can be generated in mouse tissues by an adenoviral vector expressing VEGF-A164. Once formed, four of the six types lose their VEGF-A dependency and so their responsiveness to anti-VEGF/VEGFR therapy. If therapies directed against the vasculature are to have a greater impact on human cancer, targets other than VEGF and its receptors will need to be identified on these resistant tumor vessels.