Raymond E
Presse Med. 1998;27(24):1221-4.
Work begun more than 30 years ago at Children's Hospital in Boston led to the publication of an article on the antiangiogenic properties of two compounds, endostatin and angiostatin (J. Folkman, Nature 1997; 390:404-7). It only took weeks for the medias in the US and then in France and the rest of Europe to stimulate the fervor of patients for this new 'cure' for cancer. Insight into the fundamental role of angiogenesis in locoregional and metastatic development of cancer has been accumulated over the last decades. Factors stimulating tumoral angiogenesis include aFGF, bFGF, VEGF, angiogenin, and other more recently discovered substances. Likewise, factors inhibiting tumoral angiogenesis, including angiostatin, have been identified. Angiostatin is a specific inhibitor of endothelial cell growth that migh appear rapidly in the serum of patients with a primary tumor. Angiostatin could have both local and systemic effects and possibly protect against metastatic dissemination in vivo. The importance of angiogenesis inhibitors was emphasized at the recent meeting of the American Association for Cancer Research (New Orleans March 28-April 1, 1998). To date, at least eleven compounds are being tested. Currently, most are in phase 1 or 2; for the few in phase 3, marketing approval will undoubtedly require several years. It is interesting to note that neither endostatin nor angiostatin are among the list of drugs under clinical assessment, first because these small human proteins are not available in sufficient quantity for therapeutic trials and secondly, because the processes necessary to produce pure and safe compounds remain to be developed. Even after these steps have been accomplished, preclinical evaluations will have to be performed before the first clinical trials could be envisaged. For the time being, antiangiogenesis remains a promising avenue of anti-cancer research but neither endostatin nor angiostatin will be available for human research for several months at least.
30多年前在波士顿儿童医院开展的研究促成了一篇关于两种化合物（内皮抑素和血管抑素）抗血管生成特性的文章发表（J. 福克曼，《自然》1997年；390:404 - 7）。仅过了几周，美国以及随后法国和欧洲其他地区的媒体就激发了患者对这种新“癌症疗法”的热情。在过去几十年里，人们积累了对血管生成在癌症局部和转移发展中基本作用的认识。刺激肿瘤血管生成的因素包括酸性成纤维细胞生长因子、碱性成纤维细胞生长因子、血管内皮生长因子、血管生成素以及其他一些最近发现的物质。同样，抑制肿瘤血管生成的因素，包括血管抑素，也已被确定。血管抑素是内皮细胞生长的特异性抑制剂，可能在原发性肿瘤患者的血清中迅速出现。血管抑素可能具有局部和全身作用，并有可能在体内预防转移扩散。血管生成抑制剂的重要性在最近的美国癌症研究协会会议（1998年3月28日至4月1日，新奥尔良）上得到了强调。到目前为止，至少有11种化合物正在进行测试。目前，大多数处于1期或2期；对于少数处于3期的化合物，获得上市批准无疑还需要数年时间。有趣的是，内皮抑素和血管抑素都不在临床评估的药物名单中，首先是因为这些小的人类蛋白质数量不足以进行治疗试验，其次是因为生产纯净且安全化合物所需的工艺仍有待开发。即使完成了这些步骤，在设想进行首次临床试验之前还必须进行临床前评估。目前，抗血管生成仍然是抗癌研究中一个有前景的途径，但至少在几个月内，内皮抑素和血管抑素都无法用于人体研究。
