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Int. J. Mol. Sci. 2018, 19(3), 747; https://doi.org/10.3390/ijms19030747

The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy?

1
Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, 40138 Bologna, Italy
2
Nuclear Medicine Unit, Medicina Nucleare Metropolitana, S.Orsola-Malpighi University Hospital, 40138 Bologna, Italy
3
Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, 40138 Bologna, Italy
*
Author to whom correspondence should be addressed.
Received: 30 January 2018 / Revised: 28 February 2018 / Accepted: 5 March 2018 / Published: 6 March 2018
(This article belongs to the Special Issue Cell Growth Regulation)
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Abstract

The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. The mTOR has a central converging role for many cell functions, serving as a sensor for extracellular signals from energy status and nutrients availability, growth factors, oxygen and stress. Thus, it also modulates switch to anabolic processes (protein and lipid synthesis) and autophagy, in order to regulate cell growth and proliferation. Given its functions in the cell, its deregulation is implicated in many human diseases, including cancer. Its predominant role in tumorigenesis and progression of neuroendocrine tumors (NETs), in particular, has been demonstrated in preclinical studies and late clinical trials. mTOR inhibition by everolimus is an established therapeutic target in NETs, but there are no identified predictive or prognostic factors. This review is focused on the role of mTOR and everolimus in NETs, from preclinical studies to major clinical trials, and future perspectives involving mTOR in the treatment of NETs. View Full-Text
Keywords: mTOR; neuroendocrine tumor; neuroendocrine tumors; everolimus; RAD001; RADIANT; mTORC1; PTEN; carcinoid; Akt mTOR; neuroendocrine tumor; neuroendocrine tumors; everolimus; RAD001; RADIANT; mTORC1; PTEN; carcinoid; Akt
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Lamberti, G.; Brighi, N.; Maggio, I.; Manuzzi, L.; Peterle, C.; Ambrosini, V.; Ricci, C.; Casadei, R.; Campana, D. The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy? Int. J. Mol. Sci. 2018, 19, 747.

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