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mTOR Inhibitors in Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is a genetic multiple organ system disorder that is characterized by the development of tumor-like lesions (hamartomas) and neurodevelopmental disorders. Mutations in the TSC1 and TSC2 tumor suppressor genes occur in the majority of patients with TSC, resulting in hy...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Science Publishers
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520048/ https://www.ncbi.nlm.nih.gov/pubmed/23730262 http://dx.doi.org/10.2174/157015912804143595 |
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author | Curatolo, Paolo Moavero, Romina |
author_facet | Curatolo, Paolo Moavero, Romina |
author_sort | Curatolo, Paolo |
collection | PubMed |
description | Tuberous sclerosis complex (TSC) is a genetic multiple organ system disorder that is characterized by the development of tumor-like lesions (hamartomas) and neurodevelopmental disorders. Mutations in the TSC1 and TSC2 tumor suppressor genes occur in the majority of patients with TSC, resulting in hyperactivation of the mammalian target of rapamycin (mTOR) signaling pathway and subsequent abnormalities in numerous cell processes. As a result, mTOR inhibitors such as sirolimus and everolimus have the potential to provide targeted therapy for patients with TSC. Everolimus is the first mTOR inhibitor approved as a treatment option in the USA and in Europe for patients with subependymal giant-cell astrocytomas (SEGAs) associated with TSC. The clinical evidence to date supports the use of mTOR inhibitors in a variety of TSC-associated disease manifestations, including SEGAs, renal angiomyolipoma, skin manifestations, and epilepsy. Furthermore, ongoing clinical trials evaluating mTOR inhibitors in TSC are underway, and the results of these studies are expected to provide further evidence that will firmly establish their role in this setting. This article will discuss the role of the mTOR pathway in TSC and review the pharmacokinetics, pharmacodynamics, clinical efficacy, and tolerability of mTOR inhibitors, along with their current place in clinical practice. |
format | Online Article Text |
id | pubmed-3520048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-35200482013-06-01 mTOR Inhibitors in Tuberous Sclerosis Complex Curatolo, Paolo Moavero, Romina Curr Neuropharmacol Article Tuberous sclerosis complex (TSC) is a genetic multiple organ system disorder that is characterized by the development of tumor-like lesions (hamartomas) and neurodevelopmental disorders. Mutations in the TSC1 and TSC2 tumor suppressor genes occur in the majority of patients with TSC, resulting in hyperactivation of the mammalian target of rapamycin (mTOR) signaling pathway and subsequent abnormalities in numerous cell processes. As a result, mTOR inhibitors such as sirolimus and everolimus have the potential to provide targeted therapy for patients with TSC. Everolimus is the first mTOR inhibitor approved as a treatment option in the USA and in Europe for patients with subependymal giant-cell astrocytomas (SEGAs) associated with TSC. The clinical evidence to date supports the use of mTOR inhibitors in a variety of TSC-associated disease manifestations, including SEGAs, renal angiomyolipoma, skin manifestations, and epilepsy. Furthermore, ongoing clinical trials evaluating mTOR inhibitors in TSC are underway, and the results of these studies are expected to provide further evidence that will firmly establish their role in this setting. This article will discuss the role of the mTOR pathway in TSC and review the pharmacokinetics, pharmacodynamics, clinical efficacy, and tolerability of mTOR inhibitors, along with their current place in clinical practice. Bentham Science Publishers 2012-12 2012-12 /pmc/articles/PMC3520048/ /pubmed/23730262 http://dx.doi.org/10.2174/157015912804143595 Text en ©2012 Bentham Science Publishers http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Curatolo, Paolo Moavero, Romina mTOR Inhibitors in Tuberous Sclerosis Complex |
title | mTOR Inhibitors in Tuberous Sclerosis Complex |
title_full | mTOR Inhibitors in Tuberous Sclerosis Complex |
title_fullStr | mTOR Inhibitors in Tuberous Sclerosis Complex |
title_full_unstemmed | mTOR Inhibitors in Tuberous Sclerosis Complex |
title_short | mTOR Inhibitors in Tuberous Sclerosis Complex |
title_sort | mtor inhibitors in tuberous sclerosis complex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520048/ https://www.ncbi.nlm.nih.gov/pubmed/23730262 http://dx.doi.org/10.2174/157015912804143595 |
work_keys_str_mv | AT curatolopaolo mtorinhibitorsintuberoussclerosiscomplex AT moaveroromina mtorinhibitorsintuberoussclerosiscomplex |