Dr Steven Pollard, University of Edinburgh
Paediatric glioblastoma is a devastating brain tumour that less than 20 per cent of young patients survive. This collaborative project brings together research teams from the UK, Canada and Sweden to define the role of a recently discovered genetic mutation in paediatric glioblastoma and determine whether it represents a possible target for a new therapeutic approach. The team will also create new cellular models of the disease for on-going drug-discovery efforts.
Amount of grant: £357,589 | Date of award: March 2015
Glioblastoma (GBM) is an aggressive form of brain tumour with an exceptionally poor outlook.
The cancer genes that exist in paediatric GBM have recently been identified but how they operate to drive tumour formation and growth is not understood.
Dr Pollard is working with collaborators from Canada, Sweden, London and Edinburgh, to address a fundamental unresolved issue in paediatric brain tumour research – how paediatric brain tumour cancer genes function and why they are found only in certain regions of the nervous system in children.
They are focusing on a gene called H3F3A, which is frequently mutated in paediatric GBM. It is not clear whether H3F3A mutations have an essential role in maintaining growth of tumours or whether they are only important during the earliest stages of tumour development. This is a critical issue to resolve, as it will help us understand whether drugs that target these mutations have any therapeutic value.
In this pioneering project, Dr Pollard will use state-of-the-art tools to engineer the genetic defects directly into lab grown versions of the brain cells from which the tumours are thought to arise. This will enable the team to study the function and behaviour of the cancer genes.
They will carry out experiments to determine the effect of reversing the H3F3A mutation, to see whether this represents a possible new treatment approach, and will also look at the differential effect of introducing the mutation to cells from different parts of the brain in order to determine whether tumours in different parts of the brain are truly different diseases, requiring distinct therapeutic strategies.
This work will enhance our understanding of paediatric GBM, generating vital new information about its development and giving important new insights into new treatment approaches.
Importantly, in the course of the project, the team will create new cellular models of the disease that will be freely shared with other researchers across the world, to expedite progress against this devastating disease.
About the research team
Dr Steven Pollard is a CRUK Senior Research Fellow at the University of Edinburgh. His laboratory is housed within the MRC Centre for Regenerative Medicine, which has world-class laboratory facilities and expertise, providing significant added value to the project.
In this project, Dr Pollard brings together an outstanding team of leading scientists and clinician scientists from the UK, Canada and Sweden including: Peter Dirks (The Hospital for Sick Children and University of Toronto), Helena Caren (Sahlgrenska Cancer Center, Gothenburg), Paolo Salomoni (UCL Cancer Institute, London), Paul Brennan (NHS Lothian and University of Edinburgh), Neil Carragher (Edinburgh Cancer Research Centre) and Jothy Kandasamy (NHS Lothian). As well as contributing vital, specialist scientific expertise, the collaborators also provide access to clinical material from five paediatric neurosurgical centres.
What difference will this project make?
Paediatric GBM is a devastating childhood brain tumour, which fewer than 20 per cent of patients survive. Aggressive treatments and the effects of the tumour, mean that any survivors will be left with an impaired quality of life.
This project will generate vital new information about this devastating disease. The team will define whether newly identified genetic mutations represent critical therapeutic targets and they will create a set of extremely valuable cell lines that will be shared with other researchers around the world.
Ultimately, we hope that this work will lead to the development of new treatments for children with these devastating tumours.
Read more: About childhood brain tumours | Other brain tumour research | Patient stories: brain tumours