Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation

Maria Niklison Chirou, Sara Badodi, Silvia Marino, Nicola Pomella, Xinyu Zhang, Gabriel Rosser

Research output: Contribution to journalArticlepeer-review

Abstract

Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma, the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1High;CHD7Low signature and show this can be counteracted by IP6 treatment. Finally, we demonstrate that IP6 synergises with cisplatin to enhance its cytotoxicity in vitro and extends survival in a pre-clinical BMI1High;CHD7Low xenograft model.
Original languageEnglish
Article number2148
JournalNature Communications
Volume12
DOIs
Publication statusPublished - 12 Apr 2021

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