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BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives?

IDH-wild type (wt) glioblastoma (GB) accounts for approximately 90% of all GB and has a poor outcome. Surgery and adjuvant therapy with temozolomide and radiotherapy is the main therapeutic approach. Unfortunately, after relapse and progression, which occurs in most cases, there are very limited the...

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Autores principales: Bouchè, Victoria, Aldegheri, Giovanni, Donofrio, Carmine Antonio, Fioravanti, Antonio, Roberts-Thomson, Samuel, Fox, Stephen B., Schettini, Francesco, Generali, Daniele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595319/
https://www.ncbi.nlm.nih.gov/pubmed/34804975
http://dx.doi.org/10.3389/fonc.2021.772052
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author Bouchè, Victoria
Aldegheri, Giovanni
Donofrio, Carmine Antonio
Fioravanti, Antonio
Roberts-Thomson, Samuel
Fox, Stephen B.
Schettini, Francesco
Generali, Daniele
author_facet Bouchè, Victoria
Aldegheri, Giovanni
Donofrio, Carmine Antonio
Fioravanti, Antonio
Roberts-Thomson, Samuel
Fox, Stephen B.
Schettini, Francesco
Generali, Daniele
author_sort Bouchè, Victoria
collection PubMed
description IDH-wild type (wt) glioblastoma (GB) accounts for approximately 90% of all GB and has a poor outcome. Surgery and adjuvant therapy with temozolomide and radiotherapy is the main therapeutic approach. Unfortunately, after relapse and progression, which occurs in most cases, there are very limited therapeutic options available. BRAF which plays a role in the oncogenesis of several malignant tumors, is also involved in a small proportion of IDH-wt GB. Previous successes with anti-B-Raf targeted therapy in tumors with V600E BRAF mutation like melanoma, combined with the poor prognosis and paucity of therapeutic options for GB patients is leading to a growing interest in the potential efficacy of this approach. This review is thus focused on dissecting the state of the art and future perspectives on BRAF pathway inhibition in IDH-wt GB. Overall, clinical efficacy is mostly described within case reports and umbrella trials, with promising but still insufficient results to draw more definitive conclusions. Further studies are needed to better define the molecular and phenotypic features that predict for a favorable response to treatment. In addition, limitations of B-Raf-inhibitors, in monotherapy or in combination with other therapeutic partners, to penetrate the blood-brain barrier and the development of acquired resistance mechanisms responsible for tumor progression need to be addressed.
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spelling pubmed-85953192021-11-18 BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives? Bouchè, Victoria Aldegheri, Giovanni Donofrio, Carmine Antonio Fioravanti, Antonio Roberts-Thomson, Samuel Fox, Stephen B. Schettini, Francesco Generali, Daniele Front Oncol Oncology IDH-wild type (wt) glioblastoma (GB) accounts for approximately 90% of all GB and has a poor outcome. Surgery and adjuvant therapy with temozolomide and radiotherapy is the main therapeutic approach. Unfortunately, after relapse and progression, which occurs in most cases, there are very limited therapeutic options available. BRAF which plays a role in the oncogenesis of several malignant tumors, is also involved in a small proportion of IDH-wt GB. Previous successes with anti-B-Raf targeted therapy in tumors with V600E BRAF mutation like melanoma, combined with the poor prognosis and paucity of therapeutic options for GB patients is leading to a growing interest in the potential efficacy of this approach. This review is thus focused on dissecting the state of the art and future perspectives on BRAF pathway inhibition in IDH-wt GB. Overall, clinical efficacy is mostly described within case reports and umbrella trials, with promising but still insufficient results to draw more definitive conclusions. Further studies are needed to better define the molecular and phenotypic features that predict for a favorable response to treatment. In addition, limitations of B-Raf-inhibitors, in monotherapy or in combination with other therapeutic partners, to penetrate the blood-brain barrier and the development of acquired resistance mechanisms responsible for tumor progression need to be addressed. Frontiers Media S.A. 2021-11-03 /pmc/articles/PMC8595319/ /pubmed/34804975 http://dx.doi.org/10.3389/fonc.2021.772052 Text en Copyright © 2021 Bouchè, Aldegheri, Donofrio, Fioravanti, Roberts-Thomson, Fox, Schettini and Generali https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Bouchè, Victoria
Aldegheri, Giovanni
Donofrio, Carmine Antonio
Fioravanti, Antonio
Roberts-Thomson, Samuel
Fox, Stephen B.
Schettini, Francesco
Generali, Daniele
BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives?
title BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives?
title_full BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives?
title_fullStr BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives?
title_full_unstemmed BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives?
title_short BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives?
title_sort braf signaling inhibition in glioblastoma: which clinical perspectives?
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595319/
https://www.ncbi.nlm.nih.gov/pubmed/34804975
http://dx.doi.org/10.3389/fonc.2021.772052
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