Shibuya Masabumi
Department of Molecular Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
BMB Rep. 2008 Apr 30;41(4):278-86. doi: 10.5483/bmbrep.2008.41.4.278.
Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)-VEGFRs, Angiopoietin-Tie, Ephrin-EphRs and Delta-Notch to be the major regulators of angiogenesis in vertebrates. VEGF and its receptors play a central role in physiological as well as pathological angiogenesis, and functional inhibitors of VEGF and VEGFRs such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs have recently been approved for use to treat patients with colorectal, lung, renal and liver cancers. These drugs have opened a novel field of cancer therapy, i.e. anti-angiogenesis therapy. However, as yet they cannot completely cure patients, and cancer cells could become resistant to these drugs. Thus, it is important to understand further the molecular mechanisms underlying not only VEGF-VEGFR signaling but also the VEGF-independent regulation of angiogenesis, and to learn how to improve anti-angiogenesis therapy.
血管生成，即血管的形成，对于在体内构建封闭的循环系统以及为组织提供氧气和营养至关重要。诸如癌症、类风湿性关节炎和动脉粥样硬化等主要疾病在其恶性进程中都包括病理性血管生成，这表明抗血管生成疗法是一种抑制疾病的新策略。然而，直到20世纪70年代，血管生成的分子基础在很大程度上仍是未知的。近几十年来，广泛的研究揭示了多种血管生成因子及其受体，包括血管内皮生长因子（VEGF）-VEGFRs、血管生成素-Tie、 Ephrin-EphRs和Delta-Notch，它们是脊椎动物血管生成的主要调节因子。VEGF及其受体在生理性和病理性血管生成中都起着核心作用，VEGF和VEGFRs的功能抑制剂，如抗VEGF中和抗体和阻断VEGFRs酪氨酸激酶活性的小分子，最近已被批准用于治疗结直肠癌、肺癌、肾癌和肝癌患者。这些药物开创了癌症治疗的一个新领域，即抗血管生成疗法。然而，它们目前还不能完全治愈患者，癌细胞可能会对这些药物产生耐药性。因此，进一步了解不仅VEGF-VEGFR信号传导而且血管生成的VEGF非依赖性调节的分子机制，以及学习如何改进抗血管生成疗法是很重要的。
