An exciting paper from one of the Centre’s group leaders, Dr Pathania is now published in Cancer Discovery! This was a huge effort that involved the generation of multiple models, identification of targeted therapy opportunities, and their Transatlantic partnership with collaborators. Many congratulations to the Pathania group for this fantastic research on high grade gliomas.
What did they show?
Paediatric high-grade gliomas are lethal, incurable brain tumours frequently driven by mutations in histone genes. In addition to the histone mutations these tumours also harbour partner mutations that are necessary for tumour development. These partner mutations correlate with different ages, anatomical locations, and tumour subtypes. In this paper, we developed mouse models representing 16 pHGG tumour subtypes driven by different combinations of mutations, each targeted to a region of the brain corresponding to where these tumours occur in children.
Research in the Pathania group found that the partner mutations influenced how quickly and aggressively tumours developed. They derived cell lines from these models which were able to grow in immunocompetent recipient mice, allowing rapid evaluation of experimental therapies. Using this approach they found specific drugs that were able to target pHGG cells carrying different mutation combinations. These drugs were able to reduce tumour cell spreading and extended survival in mice with brain tumours. Collectively, their models reveal that different partner mutations produce distinct effects on pHGG growth rates, invasiveness, and treatment sensitivity.