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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 9820181, 11 pages
Review Article

Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex

1Centre for Child Development, Neuropediatrics Unit, Pediatric Hospital, Coimbra Hospital and University Centre, Coimbra, Portugal
2Laboratory of Pharmacology & Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
3Centre for Neuroscience and Cell Biology-Institute for Biomedical Imaging and Life Sciences (CNC.IBILI) Research Consortium, University of Coimbra, Coimbra, Portugal

Correspondence should be addressed to Filipe Palavra; moc.liamg@arvalapepilif

Received 2 December 2016; Revised 11 February 2017; Accepted 21 February 2017; Published 12 March 2017

Academic Editor: Giuseppe Filomeni

Copyright © 2017 Filipe Palavra et al. 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.


Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of benign, noninvasive, and tumor-like lesions called hamartomas that can affect multiple organ systems and are responsible for the clinical features of the disease. In the majority of cases, TSC results from mutations in the TSC1 and TSC2 genes, leading to the overactivation of the mammalian target of rapamycin (mTOR) signalling pathway, which controls several cell functions, including cell growth, proliferation, and survival. The establishment of a connection between TSC and mTOR led to the clinical use of drugs known as mTOR inhibitors (like rapamycin, also known as sirolimus and everolimus), which are becoming an increasingly interesting tool in the management of TSC-associated features, such as subependymal giant cell astrocytomas, renal angiomyolipomas, and also epilepsy. However, the intrinsic characteristics of these drugs and their systemic effects in such a heterogeneous condition pose many challenges in clinical practice, so that some questions remain unanswered. This article provides an overview of the pharmacological aspects of mTOR inhibitors about the clinical trials leading to their approval in TSC-related conditions and exposes current challenges and future directions associated with this promising therapeutic line.