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The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?
Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor with a poor prognosis. Despite recent advances in the molecular biology of GBM, neuro-oncologists have very limited treatment options available to improve the survival of GBM patients. A prominent signaling pathway implic...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698473/ https://www.ncbi.nlm.nih.gov/pubmed/34944625 http://dx.doi.org/10.3390/biomedicines9121809 |
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author | Papavassiliou, Kostas A. Papavassiliou, Athanasios G. |
author_facet | Papavassiliou, Kostas A. Papavassiliou, Athanasios G. |
author_sort | Papavassiliou, Kostas A. |
collection | PubMed |
description | Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor with a poor prognosis. Despite recent advances in the molecular biology of GBM, neuro-oncologists have very limited treatment options available to improve the survival of GBM patients. A prominent signaling pathway implicated in GBM pathogenesis is that of the mechanistic target of rapamycin (mTOR). Attempts to target the mTOR pathway with first-generation mTOR inhibitors appeared promising in the preclinical stage; however, results have been disappointing in clinical trials, owing to the heterogeneous nature of GBM, escape mechanisms against treatment, the blood–brain barrier, drug-related toxicities, and the imperfect design of clinical trials, among others. The development of next-generation mTOR inhibitors and their current evaluation in clinical trials have sparked new hope to realize the clinical potential of mTOR inhibitors in GBM. Meanwhile, studies are continuously furthering our understanding of mTOR signaling dysregulation, its downstream effects, and interplay with other signaling pathways in GBM tumors. Therefore, it remains to be seen whether targeting mTOR in GBM will eventually prove to be fruitful or futile. |
format | Online Article Text |
id | pubmed-8698473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86984732021-12-24 The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis? Papavassiliou, Kostas A. Papavassiliou, Athanasios G. Biomedicines Opinion Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor with a poor prognosis. Despite recent advances in the molecular biology of GBM, neuro-oncologists have very limited treatment options available to improve the survival of GBM patients. A prominent signaling pathway implicated in GBM pathogenesis is that of the mechanistic target of rapamycin (mTOR). Attempts to target the mTOR pathway with first-generation mTOR inhibitors appeared promising in the preclinical stage; however, results have been disappointing in clinical trials, owing to the heterogeneous nature of GBM, escape mechanisms against treatment, the blood–brain barrier, drug-related toxicities, and the imperfect design of clinical trials, among others. The development of next-generation mTOR inhibitors and their current evaluation in clinical trials have sparked new hope to realize the clinical potential of mTOR inhibitors in GBM. Meanwhile, studies are continuously furthering our understanding of mTOR signaling dysregulation, its downstream effects, and interplay with other signaling pathways in GBM tumors. Therefore, it remains to be seen whether targeting mTOR in GBM will eventually prove to be fruitful or futile. MDPI 2021-12-01 /pmc/articles/PMC8698473/ /pubmed/34944625 http://dx.doi.org/10.3390/biomedicines9121809 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Opinion Papavassiliou, Kostas A. Papavassiliou, Athanasios G. The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis? |
title | The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis? |
title_full | The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis? |
title_fullStr | The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis? |
title_full_unstemmed | The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis? |
title_short | The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis? |
title_sort | bumpy road towards mtor inhibition in glioblastoma: quo vadis? |
topic | Opinion |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698473/ https://www.ncbi.nlm.nih.gov/pubmed/34944625 http://dx.doi.org/10.3390/biomedicines9121809 |
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