Cargando…
Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence
The mechanistic target of rapamycin (mTOR) drives several physiologic and pathologic cellular processes and is frequently deregulated in different types of tumors, including glioblastoma (GBM). Despite recent advancements in understanding the molecular mechanisms involved in GBM biology, the surviva...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312595/ https://www.ncbi.nlm.nih.gov/pubmed/30662577 http://dx.doi.org/10.1155/2018/9230479 |
_version_ | 1783383796911964160 |
---|---|
author | Mecca, Carmen Giambanco, Ileana Donato, Rosario Arcuri, Cataldo |
author_facet | Mecca, Carmen Giambanco, Ileana Donato, Rosario Arcuri, Cataldo |
author_sort | Mecca, Carmen |
collection | PubMed |
description | The mechanistic target of rapamycin (mTOR) drives several physiologic and pathologic cellular processes and is frequently deregulated in different types of tumors, including glioblastoma (GBM). Despite recent advancements in understanding the molecular mechanisms involved in GBM biology, the survival rates of this tumor are still disappointing, primarily due to the lack of efficacious treatments. The phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mTOR pathway has emerged as a crucial player in GBM development and progression. However, to date, all the attempts to target this pathway with PI3K, AKT, or mTORC1 inhibitors failed to improve the outcome of patients with GBM. Despite these discouraging results, recent evidence pointed out that the blockade of mTORC2 might provide a useful therapeutic strategy for GBM, with the potential to overcome the limitations that mTORC1 inhibitors have shown so far. In this review, we analyzed the rationale of targeting mTOR in GBM and the available preclinical and clinical evidence supporting the choice of this therapeutic approach, highlighting the different roles of mTORC1 and mTORC2 in GBM biology. |
format | Online Article Text |
id | pubmed-6312595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-63125952019-01-20 Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence Mecca, Carmen Giambanco, Ileana Donato, Rosario Arcuri, Cataldo Dis Markers Review Article The mechanistic target of rapamycin (mTOR) drives several physiologic and pathologic cellular processes and is frequently deregulated in different types of tumors, including glioblastoma (GBM). Despite recent advancements in understanding the molecular mechanisms involved in GBM biology, the survival rates of this tumor are still disappointing, primarily due to the lack of efficacious treatments. The phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mTOR pathway has emerged as a crucial player in GBM development and progression. However, to date, all the attempts to target this pathway with PI3K, AKT, or mTORC1 inhibitors failed to improve the outcome of patients with GBM. Despite these discouraging results, recent evidence pointed out that the blockade of mTORC2 might provide a useful therapeutic strategy for GBM, with the potential to overcome the limitations that mTORC1 inhibitors have shown so far. In this review, we analyzed the rationale of targeting mTOR in GBM and the available preclinical and clinical evidence supporting the choice of this therapeutic approach, highlighting the different roles of mTORC1 and mTORC2 in GBM biology. Hindawi 2018-12-18 /pmc/articles/PMC6312595/ /pubmed/30662577 http://dx.doi.org/10.1155/2018/9230479 Text en Copyright © 2018 Carmen Mecca et al. http://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 Mecca, Carmen Giambanco, Ileana Donato, Rosario Arcuri, Cataldo Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence |
title | Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence |
title_full | Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence |
title_fullStr | Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence |
title_full_unstemmed | Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence |
title_short | Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence |
title_sort | targeting mtor in glioblastoma: rationale and preclinical/clinical evidence |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312595/ https://www.ncbi.nlm.nih.gov/pubmed/30662577 http://dx.doi.org/10.1155/2018/9230479 |
work_keys_str_mv | AT meccacarmen targetingmtoringlioblastomarationaleandpreclinicalclinicalevidence AT giambancoileana targetingmtoringlioblastomarationaleandpreclinicalclinicalevidence AT donatorosario targetingmtoringlioblastomarationaleandpreclinicalclinicalevidence AT arcuricataldo targetingmtoringlioblastomarationaleandpreclinicalclinicalevidence |