Cellular and molecular effects of the mTOR inhibitor everolimus.

Saran, Uttara; Foti, Michelangelo; Dufour, Jean-François (2015). Cellular and molecular effects of the mTOR inhibitor everolimus. Clinical science, 129(10), pp. 895-914. Portland 10.1042/CS20150149

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Saran, Uttara and Dufour, Jean-François

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0143-5221

Publisher:

Portland

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

14 Apr 2016 09:17

Last Modified:

14 Apr 2016 09:17

Publisher DOI:

10.1042/CS20150149

PubMed ID:

26330617

Uncontrolled Keywords:

4E-BP1; Cancer; Drug Mechanisms of Action; Epigenetics; S6K1; Signalling; everolimus; mTOR; mTORC1; rapamycin

BORIS DOI:

10.7892/boris.77720

URI:

https://boris.unibe.ch/id/eprint/77720

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