Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Cancer Treat Rev. 2012 Nov;38(7):825-33. doi: 10.1016/j.ctrv.2012.04.006. Epub 2012 Jun 5.
It has been recognized for decades that angiogenesis is an important event in tumor growth and metastasis; the concept of the "angiogenic switch," whereby tumors acquire the ability to grow exponentially and disseminate beyond their primary site, is one of the central components in our understanding of cancer. A vast network of signaling molecules and receptors that are involved in the regulation of angiogenesis have been identified and characterized; most notably, the vascular endothelial growth factor (VEGF) family. Indeed, the VEGF family of growth factors and receptors has become a prototype for our understanding of angiogenesis during early development and in pathological conditions such as cancer. The specific inhibition of key regulatory molecules including VEGF-A (such as with bevacizumab treatment) has been recognized as a useful strategy to reduce tumor growth and progression in several tumor types. Nevertheless, the contribution of other members of the VEGF family, other signaling pathways, and also endogenous angiogenic inhibitors to tumor angiogenesis, is beginning to emerge. The diversity of pathways and molecules involved in the regulation of angiogenesis in both normal development and cancer will likely offer many more prospects for successful therapeutic intervention.
几十年来，人们已经认识到血管生成是肿瘤生长和转移的一个重要事件；“血管生成开关”的概念，即肿瘤获得指数级生长和扩散到原发部位以外的能力，是我们理解癌症的核心组成部分之一。已经鉴定和描述了大量参与血管生成调节的信号分子和受体；其中最著名的是血管内皮生长因子（VEGF）家族。事实上，VEGF 家族的生长因子和受体已成为我们理解早期发育和癌症等病理情况下血管生成的原型。包括 VEGF-A 在内的关键调节分子的特异性抑制（如贝伐单抗治疗）已被认为是减少几种肿瘤类型肿瘤生长和进展的有效策略。然而，VEGF 家族的其他成员、其他信号通路以及内源性血管生成抑制剂对肿瘤血管生成的贡献也开始显现出来。在正常发育和癌症中，参与血管生成调节的途径和分子的多样性可能为成功的治疗干预提供更多的机会。
