Center for Childhood Cancer, The Research Institute, Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
Clin Cancer Res. 2010 Mar 1;16(5):1368-72. doi: 10.1158/1078-0432.CCR-09-1314. Epub 2010 Feb 23.
Everolimus, an orally administered rapamycin analog, has recently been approved by the U.S. Food and Drug Administration for treatment of renal cell carcinoma (RCC) refractory to inhibitors of vascular endothelial growth factor (VEGF) receptor signaling. Everolimus significantly increased progression-free survival (median PFS for the everolimus treated group was 4.0 months versus 1.9 months for the placebo group), although tumor regressions were observed only infrequently. Although the target for everolimus, [the serine-threonine kinase mammalian target of rapamycin (mTOR)] is well established, the mechanism by which this agent retards tumor growth is not well defined. Further, biomarkers that predict tumor sensitivity are still elusive. The mechanism of action, preclinical antitumor activity, and clinical activity of everolimus against RCC are reviewed.
依维莫司是一种口服雷帕霉素类似物，最近已被美国食品和药物管理局批准用于治疗对血管内皮生长因子（VEGF）受体信号抑制剂耐药的肾细胞癌（RCC）。依维莫司显著延长了无进展生存期（依维莫司治疗组的中位 PFS 为 4.0 个月，安慰剂组为 1.9 个月），尽管肿瘤缓解仅偶尔观察到。尽管依维莫司的靶点[丝氨酸-苏氨酸激酶哺乳动物雷帕霉素靶蛋白（mTOR）]已经确立，但该药物延缓肿瘤生长的机制尚不清楚。此外，预测肿瘤敏感性的生物标志物仍然难以捉摸。本文综述了依维莫司治疗 RCC 的作用机制、临床前抗肿瘤活性和临床活性。
