mTOR Signaling Pathway and mTOR Inhibitors in Cancer Therapy
mTOR Signaling Pathway and mTOR Inhibitors in Cancer Therapy
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DOI：
10.1016/j.hoc.2012.02.014
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发表时间：
2012-06-01
影响因子：
2.4
通讯作者：
Ferrari, Anna C.
中科院分区：
文献类型：
--
作者：
Gomez-Pinillos, Alejandro;Ferrari, Anna C.
哺乳动物雷帕霉素靶蛋白（mTOR）是一种丝氨酸/苏氨酸蛋白激酶。它在细胞中广泛表达，是癌症治疗的治疗靶点。尽管在依赖于特定突变或mTOR通路关键成员过度激活的肿瘤中获得了很大的反应（RCC中的HiF 1 α、MCL中的细胞周期蛋白D1或SEGA中的TSC），但mTOR抑制剂作为单一药物具有适度的活性。已经开发了双重PI 3 K/mTOR激酶抑制剂，其想法是通过防止由于释放负反馈环而导致的PI 3 K/Akt的活化来克服对mTOR抑制的抗性。
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase. It is ubiquitously expressed in cells and is a therapeutic target for the cancer treatment arsenal. Despite the great responses obtained in tumors addicted to specific mutations or overactivation of key members of the mTOR pathway (HiF1 alpha in RCC, cyclin D1 in MCL, or TSC in SEGA), mTOR inhibitors as single agents have modest activity. Dual PI3K/mTOR kinase inhibitors have been developed with the idea of overcoming resistance to the mTOR inhibition through preventing the activation of PI3K/Akt as a result of release negative feedback loops.