School of Life Sciences, Swami Ramanand Teerth Marathwada University, Vishnupuri, Nanded 431606, India.
Prog Biophys Mol Biol. 2013 Nov;113(2):333-54. doi: 10.1016/j.pbiomolbio.2013.10.001. Epub 2013 Oct 15.
Angiogenesis: a process of generation of new blood vessels has been proved to be necessary for sustained tumor growth and cancer progression. Inhibiting angiogenesis pathway has long been remained a significant hope for the development of novel, effective and target orientated antitumor agents arresting the tumor proliferation and metastasis. The process of neoangiogenesis as a biological process is regulated by several pro- and anti-angiogenic factors, especially vascular endothelial growth factor, fibroblast growth factor, epidermal growth factor, hypoxia inducible factor 1 and transforming growth factor. Every endothelial cell destined for vessel formation is equipped with receptors for these angiogenic peptides. Moreover, numerous other angiogenic cytokines such as platelet derived growth factor (PGDF), placenta growth factor (PGF), nerve growth factor (NGF), stem-cell factor (SCF), and interleukins-2, 4, 6 etc. These molecular players performs critical role in regulating the angiogenic switch. Couple of decade's research in molecular aspects of tumor biology has unraveled numerous structural and functional mysteries of these angiogenic peptides. In present article, a detailed update on the functional and structural peculiarities of the various angiogenic peptides is described focusing on structural opportunities made available that has potential to be used to modulate function of these angiogenic peptides in developing therapeutic agents targeting neoplastic angiogenesis. The data may be useful in the mainstream of developing novel anticancer agents targeting tumor angiogenesis. We also discuss major therapeutic agents that are currently used in angiogenesis associated therapies as well as those are subject of active research or are in clinical trials.
新血管生成的过程已被证明是肿瘤持续生长和癌症进展所必需的。抑制血管生成途径一直是开发新型、有效和靶向抗肿瘤药物的重要希望，可以阻止肿瘤增殖和转移。新血管生成的过程作为一种生物学过程，受几种促血管生成和抗血管生成因子的调节，特别是血管内皮生长因子、成纤维细胞生长因子、表皮生长因子、缺氧诱导因子 1 和转化生长因子。每个注定要形成血管的内皮细胞都配备了这些血管生成肽的受体。此外，还有许多其他促血管生成细胞因子，如血小板衍生生长因子（PDGF）、胎盘生长因子（PGF）、神经生长因子（NGF）、干细胞因子（SCF）和白细胞介素-2、4、6 等。这些分子参与者在调节血管生成开关方面发挥着关键作用。几十年来对肿瘤生物学分子方面的研究揭示了这些血管生成肽的许多结构和功能奥秘。在本文中，详细介绍了各种血管生成肽的功能和结构特点，重点介绍了可用的结构机会，这些机会有可能用于调节这些血管生成肽的功能，以开发针对肿瘤血管生成的治疗药物。这些数据可能有助于开发针对肿瘤血管生成的新型抗癌药物的主流研究。我们还讨论了目前用于血管生成相关治疗的主要治疗药物，以及那些正在积极研究或处于临床试验阶段的药物。
