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Biol-05. Mapk Pathway Inhibition Sensitizes To Immunotherapy In Braf-mutant Gliomas by Jong-Whi Park; Anne-Marie Barrette; Wei Wang; Stefan Grossauer; Gerald Grant; Ken Lau; Sharon Pitteri; Michelle Monje; Claudia Petritsch is a Medicine article available to read on EtoBox.

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## Abstract ## Background BRAF alterations frequently occur in pediatric low-grade gliomas. Previously, we showed that dabrafenib and trametinib (D+T) that target MAPK pathway can mediate the antitumor effect in a preclinical model of BRAF-mutant glioma (PMC5342782). Here, we further investigate the effect of MAPK pathway inhibitors on cancer cells and tumor-infiltrating immune cells to maximize the therapeutic efficacy in malignant gliomas. ## Methods Drug concentrations in tumor, brain and plasma were assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RNA sequencing and Gene Set Enrichment Analysis were performed using patient-derived BRAF-mutant glioma lines upon D+T treatment. Molecular profiles of drug-resistant clones were assessed for understanding of glioma heterogeneity and exploring new therapeutic targets. Results. BRAF-mutant stem-like glioma cells were particularly resistant to BRAF or MAPK inhibitor, along with aggressive phenotype in mice. LC-MS/MS showed effective D+T drug delivery in tumor regions. The transcriptome analysis demonstrated that D+T upregulate HLA molecules and downregulate immunosuppressive factors in patient-derived BRAF-mutant g

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Author

Jong-Whi Park; Anne-Marie Barrette; Wei Wang; Stefan Grossauer; Gerald Grant; Ken Lau; Sharon Pitteri; Michelle Monje; Claudia Petritsch

Publisher

Oxford University Press (OUP)

Published

2021

Language

EN

Field

Medicine (Health Sciences)