Center of Cancer Systems Biology, Department of Medicine, St. Elizabeth's Medical Center, School of Medicine, Tufts University, Boston, MA, USA.
Dose Response. 2011;9(3):369-76. doi: 10.2203/dose-response.10-020.Javaherian. Epub 2010 Oct 21.
Angiogenesis refers to growth of blood vessels from pre-existing ones. In 1971, Folkman proposed that by choking off the blood supply to tumors, they are starved, leading to their demise. A few years ago, the monoclonal antibody Avastin became the first antiangiogenic biological approved by FDA, for treatment of cancer patients. Two other antiangiogenic endogenous protein fragments were isolated in Folkman's laboratory more than a decade ago. Here, we present a short review of data demonstrating that angiostatin and endostatin display a biphasic antitumor dose-response. This behavior is common among a large number of antiangiogenic agents and the reduced effectiveness of antiangiogenic agents at high dose rates may be due to suppression of growth of new vessels carrying the agent into the critical region around the tumor.
血管生成是指从预先存在的血管中生长出新的血管。1971 年，Folkman 提出通过阻断肿瘤的血液供应，使肿瘤饥饿，从而导致其死亡。几年前，单克隆抗体 Avastin 成为 FDA 批准的第一种抗血管生成生物制剂，用于治疗癌症患者。十多年前，Folkman 的实验室分离出另外两种抗血管生成内源性蛋白片段。在这里，我们简要回顾了一些数据，这些数据表明血管抑素和内皮抑素显示出双相抗肿瘤剂量反应。这种行为在大量抗血管生成药物中很常见，高剂量率下抗血管生成药物效果降低的原因可能是抑制了携带药物进入肿瘤周围关键区域的新血管的生长。
