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

Karisa C Schreck, Stuart A Grossman, Christine A Pratilas, Karisa C Schreck, Stuart A Grossman, Christine A Pratilas

Abstract

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.

Keywords: BRAF; BRAF V600E; MEK; astrocytoma; dabrafenib; encorafenib; glioblastoma; glioma; trametinib; vemurafenib.

Conflict of interest statement

K.C.S. and S.A.G. declare no conflict of interest. C.A.P. is a paid consultant for Genentech.

Figures

Figure 1
Figure 1
BRAF mutations found in 39 gliomas as identified from MSK-IMPACT and TCGA databases in cBioPortal displayed as a (a) lollipop plot identifying unique mutations (excluding fusions) and (b) a pie chart showing mutation types divided by class.
Figure 1
Figure 1
BRAF mutations found in 39 gliomas as identified from MSK-IMPACT and TCGA databases in cBioPortal displayed as a (a) lollipop plot identifying unique mutations (excluding fusions) and (b) a pie chart showing mutation types divided by class.

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