Response to BRAF and MEK1/2 inhibition in a young adult with BRAF V600E mutant epithelioid glioblastoma multiforme: A Case Report and Literature Review

Ashwin Venkatesh; Amol Joshi; Kieren Allinson; Tilak Das; Thomas Santarius; Sarah J Jefferies; Fiona P Harris; Rajesh Jena; Gary J Doherty

doi:10.1016/j.currproblcancer.2020.100701

Response to BRAF and MEK1/2 inhibition in a young adult with BRAF V600E mutant epithelioid glioblastoma multiforme: A Case Report and Literature Review

Curr Probl Cancer. 2021 Oct;45(5):100701. doi: 10.1016/j.currproblcancer.2020.100701. Epub 2021 Jan 12.

Authors

Ashwin Venkatesh¹, Amol Joshi¹, Kieren Allinson², Tilak Das³, Thomas Santarius⁴, Sarah J Jefferies⁵, Fiona P Harris⁵, Rajesh Jena⁶, Gary J Doherty⁷

Affiliations

¹ School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
² Department of Histopathology and Cytology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
³ Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
⁴ Department of Neurosurgery, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
⁵ Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
⁶ Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK; Department of Oncology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
⁷ Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK. Electronic address: [email protected].

PMID: 33461766
DOI: 10.1016/j.currproblcancer.2020.100701

Abstract

Epithelioid glioblastoma multiforme (eGBM) is a rare and aggressive variant of glioblastoma multiforme (GBM) that predominantly affects younger patients and can be difficult to distinguish from other gliomas. Data on how patients with eGBM might be best treated are limited, although genomic analyses have shown that almost half of tumours harbour activating BRAF gene mutations. Here we present the case of a young female with BRAF V600E-mutant eGBM who had a prolonged response to targeted therapy with the BRAF and MEK1/2 inhibitors dabrafenib and trametinib. We review current knowledge about eGBM, including the emerging role for BRAF- ± MEK1/2- targeted therapy.

Keywords: BRAF V600E mutation; Epithelioid glioblastoma multiforme; dabrafenib; targeted therapies; trametinib.

Publication types

Case Reports
Review

MeSH terms

Antineoplastic Agents / administration & dosage*
Brain Neoplasms / diagnostic imaging
Brain Neoplasms / drug therapy*
Brain Neoplasms / genetics
Brain Neoplasms / pathology
Fatal Outcome
Female
Glioblastoma / diagnostic imaging
Glioblastoma / drug therapy*
Glioblastoma / genetics
Glioblastoma / pathology
Humans
Imidazoles / administration & dosage*
MAP Kinase Kinase 1 / drug effects
MAP Kinase Kinase 2 / drug effects
Oximes / administration & dosage*
Proto-Oncogene Proteins B-raf
Pyridones / administration & dosage*
Pyridones / therapeutic use
Pyrimidinones / administration & dosage*
Pyrimidinones / therapeutic use
Spinal Cord Neoplasms / drug therapy
Spinal Cord Neoplasms / secondary
Young Adult

Substances

Antineoplastic Agents
Imidazoles
Oximes
Pyridones
Pyrimidinones
trametinib
MAP2K2 protein, human
BRAF protein, human
Proto-Oncogene Proteins B-raf
MAP Kinase Kinase 1
MAP Kinase Kinase 2
MAP2K1 protein, human
dabrafenib