Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation.
Julian SteiningerC BuszelloR OertelM MeinhardtS SchmidK EngellandtS HeroldS StasikA EbrahimiB RennerC ThiedeI Y EyüpogluG SchackertS BeissertF MeierJ RadkeD WestphalT A JuratliPublished in: Acta neuropathologica communications (2024)
Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.
Keyphrases
- protein kinase
- cerebrospinal fluid
- liquid chromatography tandem mass spectrometry
- pi k akt
- signaling pathway
- tyrosine kinase
- case report
- oxidative stress
- healthcare
- public health
- single cell
- simultaneous determination
- ms ms
- metastatic colorectal cancer
- cell therapy
- drug delivery
- genome wide
- multiple sclerosis
- gene expression
- health information
- copy number
- circulating tumor
- cancer therapy
- bone marrow
- transcription factor
- climate change
- mass spectrometry
- replacement therapy