Modes of resistance to anti-angiogenic therapy.
Modes of resistance to anti-angiogenic therapy.
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DOI：
10.1038/nrc2442
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发表时间：
2008-08
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针对血管内皮生长因子(VEGF)信号通路的血管生成抑制剂在小鼠癌症模型和越来越多的人类癌症中提供了明显的治疗效果。然而，在临床前和临床环境中，益处充其量是暂时的，随后是肿瘤生长和进展的恢复。新出现的数据支持这样一个命题，即有两种非常规抵抗模式构成了这种结果的基础：逃避抵抗，一种绕过特定血管生成障碍的适应；以及内在或先前存在的冷漠。多种机制可以在不同的肿瘤环境中被调用，以显示回避和内在耐药，激励对其流行率和重要性的评估，进而设计提供持久抗血管生成治疗的药理学策略。
Angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signalling pathways are affording demonstrable therapeutic efficacy in mouse models of cancer and in an increasing number of human cancers. However, in both preclinical and clinical settings, the benefits are at best transitory and are followed by a restoration of tumour growth and progression. Emerging data support a proposition that two modes of unconventional resistance underlie such results: evasive resistance, an adaptation to circumvent the specific angiogenic blockade; and intrinsic or pre-existing indifference. Multiple mechanisms can be invoked in different tumour contexts to manifest both evasive and intrinsic resistance, motivating assessment of their prevalence and importance and in turn the design of pharmacological strategies that confer enduring anti-angiogenic therapies.