Xie Jianling, Wang Xuemin, Proud Christopher G
Nutrition and Metabolism, South Australian Health and Medical research Institute, Adelaide, SA, Australia.
Nutrition and Metabolism, South Australian Health and Medical research Institute, Adelaide, SA, Australia; School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
F1000Res. 2016 Aug 25;5. doi: 10.12688/f1000research.9207.1. eCollection 2016.
The mammalian target of rapamycin, mTOR, plays key roles in cell growth and proliferation, acting at the catalytic subunit of two protein kinase complexes: mTOR complexes 1 and 2 (mTORC1/2). mTORC1 signaling is switched on by several oncogenic signaling pathways and is accordingly hyperactive in the majority of cancers. Inhibiting mTORC1 signaling has therefore attracted great attention as an anti-cancer therapy. However, progress in using inhibitors of mTOR signaling as therapeutic agents in oncology has been limited by a number of factors, including the fact that the classic mTOR inhibitor, rapamycin, inhibits only some of the effects of mTOR; the existence of several feedback loops; and the crucial importance of mTOR in normal physiology.
雷帕霉素的哺乳动物靶点，即mTOR，在细胞生长和增殖中发挥关键作用，作用于两种蛋白激酶复合物的催化亚基：mTOR复合物1和2（mTORC1/2）。mTORC1信号传导由多种致癌信号通路激活，因此在大多数癌症中处于过度活跃状态。因此，抑制mTORC1信号传导作为一种抗癌疗法已引起广泛关注。然而，将mTOR信号抑制剂用作肿瘤治疗药物的进展受到多种因素的限制，包括经典的mTOR抑制剂雷帕霉素仅抑制mTOR的部分作用；存在多个反馈回路；以及mTOR在正常生理学中的至关重要性。
