Low-grade glioma is a rare brain tumour that predominantly affects teenagers and young adults. There is no cure and all patients ultimately progress to high-grade glioma, at which point their prognosis is around two years.
In this project, neurosurgeon Richard Mair wants to block low-grade to high-grade progression and therefore improve prognosis in this young patient group.
Following rigorous assessment as part of our competitive grant round, this project was recommended for its importance in this under-resourced area of research, with potential to improve prognosis for many young patients.
Low-grade glioma (LGG) is a rare brain cancer that predominantly affects teenagers and young adults. There is no cure, and no new treatments have been developed for decades. Current treatment consists of surgery for diagnosis and to ‘debulk’ the tumour, followed by radiotherapy and then a prolonged surveillance period using MRI.
Despite the prolonged period of surveillance, which aims to detect tumour progression, there are no treatments that can halt this progression when it occurs. All patients with LGG will ultimately progress into high-grade glioma (HGG) at which point their prognosis is around two years.
Mr Mair proposes that the prolonged surveillance period in people with LGG is a perfect time during which to intervene. He believes that patient prognosis could be extended significantly by intervening whilst the cancer remains low-grade, rather than waiting for it to progress.
Little is known about how and why patients with LGG progress to HGG and there are no treatments that block this progression. This is the focus of Mr Mair's project.
LGG is commonly associated with a mutation to a gene called IDH within a patient’s brain cells. This mutation affects the way that a cancer cell makes energy (its metabolism). We know that this altered metabolism causes many changes to the way that genes are controlled within the tumour cells.
We also know that these cancers become starved of oxygen as they grow. Mr Mair hypothesises that the lack of oxygen in the context of the metabolic and gene changes found within LGG drive progression of the tumour.
In this project, he will use multiple methods to investigate these changes and identify the molecular causes of the progression of LGG. His multi-pronged approach includes the development and validation of a new mouse model for the study of LGG, and analysis of patient-derived brain tumour samples from the operating theatre.
This will give new insight to the molecular causes of the progression of LGG, and enable the identification of therapeutic targets. Drugs can then be developed (or repurposed) against these targets to halt progression.
Despite the team’s access to human brain tumour samples, it is necessary to use animals (mice) in this research. The brain environment in which the transformation from LGG to HGG occurs is too complex to model outside of the living brain, and the changes that occur over time cannot be reproduced from static analysis of human samples. Therefore it is necessary to use model systems that better represent the complex, dynamic environment of LGG transformation.
The team has performed careful calculations using their extensive experience in developing this technique to minimise the number of animals required.
The use of animals is specifically addressed as part of our review process, to make sure that the use of animals is necessary, relevant and well-designed. All animal research carried out in the UK is tightly regulated by the Home Office and we require copies of the relevant licences before work can get underway.
This project represents a key step on the pathway towards the identification or development of drugs that could block the progression from low-grade to high-grade glioma.
Mr Richard Mair is an Honorary Consultant Neurosurgeon at Addenbrooke’s Hospital and a Lecturer in Neurosurgical Oncology at the University of Cambridge. He has extensive experience in the range of research techniques required in this project.
He is working with Dr Manav Pathania, a world expert on mouse models of glioma, who pioneered the technology that will be used for the generation for the mouse model of LGG.
Together this team is well-placed to succeed in the delivery of this important and ambitious project.
Brain tumours are one of our current research priorities, reflecting the large unmet need in this area. Our aim is to fund research to advance understanding of the causes and underlying mechanisms of brain tumours, and help us to diagnose and treat them more effectively.
Other research projects currently funded under this theme:
Find out about our other research in this area: