mTOR inhibitors in cancer therapy [version 1; referees: 3 approved]

• Main Authors: Jianling Xie, Xuemin Wang, Christopher G. Proud
• Format: Article
• Language: English
• Published: F1000 Research Ltd 2016-08-01
• Series: F1000Research
• Subjects: Cancer Therapeutics; Cell Growth & Division; Cell Signaling; Control of Gene Expression; Drug Discovery & Design; Medical Genetics; Membranes & Sorting; Pharmacokinetics & Drug Delivery
• Online Access: http://f1000research.com/articles/5-2078/v1

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.