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

Lookup NU author(s): Professor Steven CliffordORCiD

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Abstract

© 2021, The Author(s).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.

Publication metadata

Author(s): Badodi S, Pomella N, Zhang X, Rosser G, Whittingham J, Niklison-Chirou MV, Lim YM, Brandner S, Morrison G, Pollard SM, Bennett CD, Clifford SC, Peet A, Basson MA, Marino S

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2021

Volume: 12

Issue: 1

Online publication date: 12/04/2021

Acceptance date: 12/03/2021

Date deposited: 07/11/2023

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-021-22379-7

DOI: 10.1038/s41467-021-22379-7

PubMed id: 33846320

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