Bergers Gabriele, Hanahan Douglas
University of California, San Francisco, Department of Neurological Surgery, Brain Tumour Research Center, San Francisco, California 94143, USA.
Nat Rev Cancer. 2008 Aug;8(8):592-603. doi: 10.1038/nrc2442.
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.
靶向血管内皮生长因子（VEGF）信号通路的血管生成抑制剂在癌症小鼠模型以及越来越多的人类癌症中显示出明显的治疗效果。然而，在临床前和临床环境中，这些益处充其量只是暂时的，随后肿瘤会恢复生长和进展。新出现的数据支持这样一种观点，即两种非常规耐药模式是导致这种结果的基础：逃避性耐药，即一种规避特定血管生成阻断的适应性反应；以及内在或预先存在的无反应性。在不同的肿瘤背景下，可以调用多种机制来表现逃避性和内在耐药性，这促使人们评估它们的普遍性和重要性，进而设计出能够提供持久抗血管生成治疗的药理学策略。
