mTOR (mechanistic target of rapamycin) functions as the central regulator for cell proliferation, growth and survival. Up-regulation of proteins regulating mTOR, as well as its downstream targets, has been reported in various cancers. This has promoted the development of anti-cancer therapies targeting mTOR, namely fungal macrolide rapamycin, a naturally occurring mTOR inhibitor, and its analogues (rapalogues). One such rapalogue, everolimus, has been approved in the clinical treatment of renal and breast cancers. Although results have demonstrated that these mTOR inhibitors are effective in attenuating cell growth of cancer cells under in vitro and in vivo conditions, subsequent sporadic response to rapalogues therapy in clinical trials has promoted researchers to look further into the complex understanding of the dynamics of mTOR regulation in the tumour environment. Limitations of these rapalogues include the sensitivity of tumour subsets to mTOR inhibition. Additionally, it is well known that rapamycin and its rapalogues mediate their effects by inhibiting mTORC (mTOR complex) 1, with limited or no effect on mTORC2 activity. The present review summarizes the pre-clinical, clinical and recent discoveries, with emphasis on the cellular and molecular effects of everolimus in cancer therapy.
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Review Article|
September 01 2015
Cellular and molecular effects of the mTOR inhibitor everolimus
Uttara Saran;
Uttara Saran
*Hepatology, Department of Clinical Research, University of Berne, Switzerland
†University Clinic of Visceral Surgery and Medicine, Inselspital, Berne, Switzerland
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Michelangelo Foti;
Michelangelo Foti
‡Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
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Jean-François Dufour
*Hepatology, Department of Clinical Research, University of Berne, Switzerland
†University Clinic of Visceral Surgery and Medicine, Inselspital, Berne, Switzerland
Correspondence: Professor Jean-François Dufour (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 18 2015
Revision Received:
July 01 2015
Accepted:
July 22 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2015 Authors; published by Portland Press Limited
2015
Clin Sci (Lond) (2015) 129 (10): 895–914.
Article history
Received:
February 18 2015
Revision Received:
July 01 2015
Accepted:
July 22 2015
Citation
Uttara Saran, Michelangelo Foti, Jean-François Dufour; Cellular and molecular effects of the mTOR inhibitor everolimus. Clin Sci (Lond) 1 November 2015; 129 (10): 895–914. doi: https://doi.org/10.1042/CS20150149
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