Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33846320.
- Also identified by DOI 10.1038/s41467-021-22379-7 and PMC identifier 8042111.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 BMI1<sup>High</sup>;CHD7<sup>Low</sup> 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 BMI1<sup>High</sup>;CHD7<sup>Low</sup> xenograft model.
Medical subject headings
- Adaptation, Physiological
- Cerebellar Neoplasms
- Epigenesis, Genetic
- Inositol
- Medulloblastoma