Will mTOR inhibitors make it as cancer drugs?
Will mTOR inhibitors make it as cancer drugs?
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DOI：
10.1016/s1535-6108(03)00275-7
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发表时间：
2003-11-01
期刊：
影响因子：
50.3
通讯作者：
Sawyers, CL
中科院分区：
文献类型：
--
作者：
Sawyers, CL
344癌细胞：2003年11月的筛选研究揭示了雷帕霉素作为抗增殖剂的广泛潜力，但他们没有揭示其机制。尽管如此，结果确定了两组雷帕霉素敏感的细胞系-那些响应与mTOR抑制（1 nM）相关的细胞系（第1组）和那些需要显着更高浓度的细胞系（第2组）。值得注意的是，第2组细胞系对低“剂量”（InM）雷帕霉素应答的失败不能用mTOR激酶活性的不充分阻断来解释，因为InM雷帕霉素在两组中抑制S6 K和4 EBP 1磷酸化是同样有效的（Neshat等人，2001年）。这些数据支持这样的观点，即mTOR是第1组中肿瘤系的雷帕霉素的生物学相关靶标，而其他靶标在第2组中是相关的。
344 CANCER CELL: NOVEMBER 2003 screening studies revealed the broad potential for rapamycin as an antiproliferative agent, they did not uncover the mechanism. Nonetheless, the results define two groups of rapamycin-sensitive cell lines—those whose response correlates with inhibition of mTOR (1 nM)(group 1) and those that require significantly higher concentrations (group 2). Of note, the failure of the group 2 cell lines to respond to low “dose”(1 nM) rapamycin cannot be explained by insufficient blockade of mTOR kinase activity because 1 nM rapamycin was equally effective at inhibiting S6K and 4EBP1 phosphorylation in both groups (Neshat et al., 2001). These data support the notion that mTOR is the biologically relevant target of rapamycin for the tumor lines in group 1, whereas other targets are relevant in group 2.