Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Papavassiliou, Kostas A., Papavassiliou, Athanasios G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784620287956877312
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
work_keys_str_mv AT papavassilioukostasa thebumpyroadtowardsmtorinhibitioninglioblastomaquovadis
AT papavassiliouathanasiosg thebumpyroadtowardsmtorinhibitioninglioblastomaquovadis
AT papavassilioukostasa bumpyroadtowardsmtorinhibitioninglioblastomaquovadis
AT papavassiliouathanasiosg bumpyroadtowardsmtorinhibitioninglioblastomaquovadis