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Recent insights into the pathophysiology of mTOR pathway dysregulation

Authors Gitto SB, Altomare DA

Received 25 October 2014

Accepted for publication 11 December 2014

Published 29 January 2015 Volume 2015:6 Pages 1—16

DOI https://doi.org/10.2147/RRB.S57088

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Professor Zvi Kelman

Sarah B Gitto, Deborah A Altomare

Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA

Abstract: Mechanistic target of rapamycin (mTOR) dysregulation is present in a variety of human pathologies including neurological disease, cancer, diabetes, and cardiac disease. Hyperactivation leads to increased protein synthesis and cell growth, which are essential for growth, development, and cancer. Inhibition of mTOR results in induction of autophagy, a cell survival mechanism thought to be deficient in neurodegeneration. Counteracting the balance of mTOR signaling with target specific inhibitors is of interest in pathological conditions where mTOR signaling is upregulated. The US Food and Drug Administration (FDA) has approved the use of rapamycin for treatment of renal cell, pancreatic neuroendocrine, and hormone positive breast cancer. Many clinical trials are underway to determine the efficacy of mTOR inhibitors in other pathologies as monotherapies or combinational therapies with chemotherapeutics, tyrosine kinase inhibitors, molecular targeted therapies, and vascular endothelial growth factor (VEGF) inhibitors. Collectively, this review is an overview of the current practices and outcomes of pharmaceutically targeting this highly studied mediator of normal and aberrant cell function.

Keywords: signal transduction, small molecule inhibitors, translational impact, neurological diseases, cardiovascular disorders, diabetes, cancer

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