Research And Grants

Unravelling transcriptional plasticity as a non-genetic mechanism of drug resistance in DMG.

Diffuse midline glioma (DMG) is a malignant brain tumour arising in children representing a major unmet clinical need, with a 2-year survival rate close to zero. We and others have found that some DMGs have alterations in the MAPK pathway which drives cell growth – drugs targeting this pathway may be initially effective, but eventually the cancer cells escape therapy. We have used DMG cell models to show that this drug resistance can occur in a new way, in which cells slow down and ‘hide’ from drug treatment by temporarily changing their make up in a way that makes the drug ineffective. Having shown that this can occur, we now wish to learn more about DMG cells pull of this trick, by growing them in the lab and determining the precise mechanism that allows them to tolerate exposure to drug. Having done so, we hope to find ways of overcoming it that might be a useful and much-needed therapeutic strategy for children with these tumours.