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Lookup NU author(s): Professor Steven Clifford
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© 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.
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
Online publication date: 12/04/2021
Acceptance date: 12/03/2021
ISSN (electronic): 2041-1723
Publisher: Nature Research
PubMed id: 33846320
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