Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
Semin Cancer Biol. 2009 Oct;19(5):329-37. doi: 10.1016/j.semcancer.2009.05.003. Epub 2009 May 29.
Coined in the late eighties, the term "angiogenic switch" refers to a time-restricted event during tumor progression where the balance between pro- and anti-angiogenic factors tilts towards a pro-angiogenic outcome, resulting in the transition from dormant avascularized hyperplasia to outgrowing vascularized tumor and eventually to malignant tumor progression. The molecular players and mechanisms underlying the angiogenic switch have been intensely investigated. In particular, a large number of pro-angiogenic factors and angiogenic inhibitors activated and repressed, respectively, in their activities during the angiogenic switch have been identified and characterized. Part of this research has lead to the development of various pro- and anti-angiogenic therapies that are currently tested in clinical trials or are already in clinical use. More recently, transgenic mouse models of cancer have been instrumental in revealing that inflammatory responses within the tumor microenvironment are critically contributing to the onset of tumor angiogenesis. These mouse models closely recapitulate multistage carcinogenesis in cancer patients and represent reliable tools to study the molecular and cellular players implicated in the onset and maintenance of tumor angiogenesis. Furthermore, they also offer the opportunity to assess the efficacy of novel anti-angiogenic cancer therapies and the nature of developing resistance mechanisms. These experiments have provided first important concepts to improve anti-angiogenic therapy and thus directly contribute to their translation to the clinical setting.
“血管生成开关”一词是在 80 年代后期提出的，它指的是肿瘤进展过程中一个时间受限的事件，在此期间，促血管生成和抗血管生成因子之间的平衡倾向于促血管生成的结果，导致从休眠的无血管增生向过度生长的血管化肿瘤的转变，最终发展为恶性肿瘤进展。血管生成开关背后的分子机制和分子参与者已经得到了深入研究。特别是，已经鉴定和表征了大量的促血管生成因子和血管生成抑制剂，它们在血管生成开关期间分别被激活和抑制。部分研究已经导致了各种促血管生成和抗血管生成疗法的发展，这些疗法目前正在临床试验中进行测试，或者已经在临床应用中。最近，癌症的转基因小鼠模型在揭示肿瘤微环境中的炎症反应对肿瘤血管生成的发生起着至关重要的作用方面发挥了重要作用。这些小鼠模型非常类似于癌症患者的多阶段致癌过程，是研究肿瘤血管生成起始和维持所涉及的分子和细胞参与者的可靠工具。此外，它们还提供了评估新型抗血管生成癌症疗法疗效和开发耐药机制的机会。这些实验提供了改善抗血管生成治疗的重要概念，因此直接有助于将其转化为临床环境。
