Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation.
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Volume
12
Publisher
Publisher URL
DOI
10.1038/s41467-021-22379-7
Journal
Nature Communications
ISSN
2041-1723
Metadata
Show full item recordAbstract
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.