Why do we need accurate models?
Accurate models are important to advance our understanding of the basic biology of paediatric brain tumours such as how the tumours develop and grow. These models include cell lines, genetically engineered mouse models (GEMMs) and patient-derived orthotopic xenografts (PDOXs).We perform techniques such as single cell sequencing to find out what is causing the tumours to grow. Doing these experiments will help identify the cellular origins of these tumours and discover genetic drivers and cell hierarchies that maintain the tumours. Understanding what drives tumour growth can lead to discovery of new drug targets which can be used to develop medicines to kill cancer cells. These models are also needed to accurately assess therapies pre-clinically to enable a better understanding of how potential therapies might work in patients.
Who is working on these models?
This biological work is a key focus of the Centre and is carried out by the Gilbertson and Pathania Labs (Cambridge) and the Jones and Chesler groups (ICR). Work includes modelling high grade glioma, ependymoma, medulloblastoma and choroid plexus carcinoma.
What are our ongoing projects?
These models are used to understand how tumours grow and develop and can also provide insight into the origin of the tumour itself too. Current projects in the Gilbertson lab focused on developing models for ependymoma, choroid plexus carcinoma and WNT-medulloblastoma. Work in the Pathania lab is focused on modelling the key mutations found in high grade gliomas. Lab techniques such as immunohistochemistry (staining tumour sections to see cancer markers and structures) and single cell sequencing help to provide a good picture of how the tumour develops. Sigourney Bonner, a PhD student in the centre has developed the first spontaneous model of ZFTA-RELA fusion driven ependymoma. Please read more about the ependymoma project at the Centre where the models will be used to assess how the new therapies are working alongside current standard of care treatment.