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

Sara Badodi, Nicola Pomella, Xinyu Zhang, Gabriel Rosser, John Whittingham, Maria Niklison Chirou, Yau Mun Lim, Sebastian Brandner, Steven M. Pollard, Christopher D. Bennett, Steven C. Clifford, Andrew Peet, Albert Basson, Silvia Marino

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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