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BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors

BRAF mutations have been identified as targetable, oncogenic mutations in many cancers. Given the paucity of treatments for primary brain tumors and the poor prognosis associated with high-grade gliomas, BRAF mutations in glioma are of considerable interest. In this review, we present the spectrum o...

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Autores principales: Schreck, Karisa C., Grossman, Stuart A., Pratilas, Christine A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769482/
https://www.ncbi.nlm.nih.gov/pubmed/31466300
http://dx.doi.org/10.3390/cancers11091262
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author Schreck, Karisa C.
Grossman, Stuart A.
Pratilas, Christine A.
author_facet Schreck, Karisa C.
Grossman, Stuart A.
Pratilas, Christine A.
author_sort Schreck, Karisa C.
collection PubMed
description BRAF mutations have been identified as targetable, oncogenic mutations in many cancers. Given the paucity of treatments for primary brain tumors and the poor prognosis associated with high-grade gliomas, BRAF mutations in glioma are of considerable interest. In this review, we present the spectrum of BRAF mutations and fusion alterations present in each class of primary brain tumor based on publicly available databases and publications. We also summarize clinical experience with RAF and MEK inhibitors in patients with primary brain tumors and describe ongoing clinical trials of RAF inhibitors in glioma. Sensitivity to RAF and MEK inhibitors varies among BRAF mutations and between tumor types as only class I BRAF V600 mutations are sensitive to clinically available RAF inhibitors. While class II and III BRAF mutations are found in primary brain tumors, further research is necessary to determine their sensitivity to third-generation RAF inhibitors and/or MEK inhibitors. We recommend that the neuro-oncologist consider using these drugs primarily in the setting of a clinical trial for patients with BRAF-altered glioma in order to advance our knowledge of their efficacy in this patient population.
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spelling pubmed-67694822019-10-30 BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors Schreck, Karisa C. Grossman, Stuart A. Pratilas, Christine A. Cancers (Basel) Review BRAF mutations have been identified as targetable, oncogenic mutations in many cancers. Given the paucity of treatments for primary brain tumors and the poor prognosis associated with high-grade gliomas, BRAF mutations in glioma are of considerable interest. In this review, we present the spectrum of BRAF mutations and fusion alterations present in each class of primary brain tumor based on publicly available databases and publications. We also summarize clinical experience with RAF and MEK inhibitors in patients with primary brain tumors and describe ongoing clinical trials of RAF inhibitors in glioma. Sensitivity to RAF and MEK inhibitors varies among BRAF mutations and between tumor types as only class I BRAF V600 mutations are sensitive to clinically available RAF inhibitors. While class II and III BRAF mutations are found in primary brain tumors, further research is necessary to determine their sensitivity to third-generation RAF inhibitors and/or MEK inhibitors. We recommend that the neuro-oncologist consider using these drugs primarily in the setting of a clinical trial for patients with BRAF-altered glioma in order to advance our knowledge of their efficacy in this patient population. MDPI 2019-08-28 /pmc/articles/PMC6769482/ /pubmed/31466300 http://dx.doi.org/10.3390/cancers11091262 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Schreck, Karisa C.
Grossman, Stuart A.
Pratilas, Christine A.
BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors
title BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors
title_full BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors
title_fullStr BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors
title_full_unstemmed BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors
title_short BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors
title_sort braf mutations and the utility of raf and mek inhibitors in primary brain tumors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769482/
https://www.ncbi.nlm.nih.gov/pubmed/31466300
http://dx.doi.org/10.3390/cancers11091262
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