PMID- 28386314
OWN - NLM
STAT- MEDLINE
DCOM- 20170523
LR  - 20211204
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2017
DP  - 2017
TI  - Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of 
      Patients with Tuberous Sclerosis Complex.
PG  - 9820181
LID - 10.1155/2017/9820181 [doi]
LID - 9820181
AB  - 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.
FAU - Palavra, Filipe
AU  - Palavra F
AUID- ORCID: 0000-0002-2165-130X
AD  - Centre for Child Development, Neuropediatrics Unit, Pediatric Hospital, Coimbra 
      Hospital and University Centre, Coimbra, Portugal; Laboratory of Pharmacology & 
      Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences 
      (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
FAU - Robalo, Conceicao
AU  - Robalo C
AD  - Centre for Child Development, Neuropediatrics Unit, Pediatric Hospital, Coimbra 
      Hospital and University Centre, Coimbra, Portugal.
FAU - Reis, Flavio
AU  - Reis F
AUID- ORCID: 0000-0003-3401-9554
AD  - Laboratory of Pharmacology & Experimental Therapeutics, Institute for Biomedical 
      Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 
      Coimbra, Portugal; Centre for Neuroscience and Cell Biology-Institute for 
      Biomedical Imaging and Life Sciences (CNC.IBILI) Research Consortium, University 
      of Coimbra, Coimbra, Portugal.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170312
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Enzyme Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Enzyme Inhibitors/pharmacology/*therapeutic use
MH  - Humans
MH  - Molecular Structure
MH  - Pharmacology/standards/trends
MH  - Sirolimus/chemistry/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Tuberous Sclerosis/*drug therapy
PMC - PMC5366202
EDAT- 2017/04/08 06:00
MHDA- 2017/05/24 06:00
PMCR- 2017/03/12
CRDT- 2017/04/08 06:00
PHST- 2016/12/02 00:00 [received]
PHST- 2017/02/11 00:00 [revised]
PHST- 2017/02/21 00:00 [accepted]
PHST- 2017/04/08 06:00 [entrez]
PHST- 2017/04/08 06:00 [pubmed]
PHST- 2017/05/24 06:00 [medline]
PHST- 2017/03/12 00:00 [pmc-release]
AID - 10.1155/2017/9820181 [doi]
PST - ppublish
SO  - Oxid Med Cell Longev. 2017;2017:9820181. doi: 10.1155/2017/9820181. Epub 2017 Mar 
      12.