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Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex
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 mutat...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366202/ https://www.ncbi.nlm.nih.gov/pubmed/28386314 http://dx.doi.org/10.1155/2017/9820181 |
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author | Palavra, Filipe Robalo, Conceição Reis, Flávio |
author_facet | Palavra, Filipe Robalo, Conceição Reis, Flávio |
author_sort | Palavra, Filipe |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5366202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-53662022017-04-06 Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex Palavra, Filipe Robalo, Conceição Reis, Flávio Oxid Med Cell Longev Review Article 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. Hindawi 2017 2017-03-12 /pmc/articles/PMC5366202/ /pubmed/28386314 http://dx.doi.org/10.1155/2017/9820181 Text en Copyright © 2017 Filipe Palavra et al. https://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Review Article Palavra, Filipe Robalo, Conceição Reis, Flávio Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex |
title | Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex |
title_full | Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex |
title_fullStr | Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex |
title_full_unstemmed | Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex |
title_short | Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex |
title_sort | recent advances and challenges of mtor inhibitors use in the treatment of patients with tuberous sclerosis complex |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366202/ https://www.ncbi.nlm.nih.gov/pubmed/28386314 http://dx.doi.org/10.1155/2017/9820181 |
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