Folkman Judah
Children's Hospital/Harvard Medical School, Cambridge, MA, USA.
Exp Cell Res. 2006 Mar 10;312(5):594-607. doi: 10.1016/j.yexcr.2005.11.015. Epub 2005 Dec 22.
The first angiogenesis inhibitors for cancer have now been approved by the F.D.A. in the U.S. and in 28 other countries, including China. The majority of these are monotherapies that block VEGF. However, mutant tumor cells may over time produce redundant angiogenic factors. Therefore, for long-term use in cancer, combinations of angiogenesis inhibitors or broad spectrum angiogenesis inhibitors will be needed. The two most broad spectrum and least toxic angiogenesis inhibitors are Caplostatin and endostatin. Endostatin inhibits 65 different tumor types and modifies 12% of the human genome to downregulate pathological angiogenesis without side-effects. The recent discovery that small increases in circulating endostatin can suppress tumor growth and that orally available small molecules can increase endostatin in the plasma suggests the possible development of a new pharmaceutical field.
首批用于癌症治疗的血管生成抑制剂现已获美国食品药品监督管理局（F.D.A.）以及包括中国在内的其他28个国家批准。其中大多数是阻断血管内皮生长因子（VEGF）的单一疗法。然而，随着时间推移，突变的肿瘤细胞可能会产生多余的血管生成因子。因此，对于癌症的长期治疗，将需要血管生成抑制剂的联合用药或广谱血管生成抑制剂。两种最具广谱性且毒性最小的血管生成抑制剂是卡泊他汀和内皮抑素。内皮抑素可抑制65种不同的肿瘤类型，并改变人类基因组的12%以下调病理性血管生成，且无副作用。最近的发现表明，循环内皮抑素的小幅增加可抑制肿瘤生长，并且口服小分子药物可提高血浆中的内皮抑素水平，这预示着一个新的制药领域有可能得到发展。
