Glioblastoma is an aggressive, incurable type of brain tumour that strikes around 2,500 people every year in the UK. Only a quarter of patients survive more than a year from diagnosis.
In this project, Dr Gomez-Roman is pursuing a new avenue of research, focused on the importance of cholesterol on the growth and survival of glioblastoma cells.
Following rigorous assessment as part of our competitive grant round, this project was recommended for its promising, as yet unexplored, approach to glioblastoma therapy.
Glioblastoma is an aggressive, invasive tumour that grows and spreads quickly and infiltrates the brain. Despite many years of research, the treatments developed in the laboratory have failed to improve patient outcomes and glioblastoma remains incurable.
The current treatment strategy includes surgery to ‘debulk’ the tumour, followed by radiotherapy and chemotherapy to destroy remaining tumour. This prolongs survival but is not curative - the tumour always grows back. Only a quarter of patients survive more than a year from diagnosis, and just 5% survive five years.
Treatment resistance is attributed to cells called glioma stem-like cells (GSC), which evade therapy and drive the formation of new tumours. Finding a way to target these cells is key to the effective treatment of glioblastoma.
Cholesterol is a fatty substance that our bodies need but is damaging if present at a high level; its association with heart disease is well-established. Recent studies have revealed that it also plays a role in glioblastoma; glioblastoma cells have unusually high levels of cholesterol and rely on it to survive.
When glioblastoma cells have too much cholesterol, they grow faster and become more resistant to chemotherapy and radiation. Dr Gomez-Roman and others have found that targeting the movement of cholesterol within cells is very effective at killing glioblastoma cells in the laboratory.
The team’s preliminary findings show that genes and proteins involved in cholesterol movement are expressed at increased levels in glioblastoma tumours compared to normal brain tissue. This increased expression is linked to a worse prognosis. Additionally, they have found that genes involved in cholesterol movement are more active in GSCs compared to other glioblastoma cells. This suggests a connection between cholesterol movement and tumour growth.
In this project, Dr Gomez-Roman and team will study the storage and movement of cholesterol in glioblastoma and normal brain cells. They will inhibit certain genes that regulate cholesterol movement, and will study the effect on glioblastoma cells and normal brain cells. They want to understand how this inhibition – either alone or in combination with radiation and chemotherapy – works, and how it causes cell death.
They will investigate whether proteins involved in cholesterol movement affect the formation and growth of glioblastoma tumours in laboratory models of glioblastoma, and will see whether inhibiting these proteins, in combination with radiation and chemotherapy, can help the mice live longer.
Glioblastoma is a devastating brain tumour, with average survival of just 12 to 18 months.
In this project the team will be exploring a new treatment approach targeting cholesterol in glioblastoma cells. By combining this approach with standard care, the hope is that patient survival will be improved. In this field where treatment options have remained static for two decades, this work is critically important.
Dr Natividad Gomez-Roman has extensive experience in this kind of research, developing and applying pre-clinical models, screening candidate compounds, and radiation biology. She has good understanding of the progression of compounds from the bench to the clinic.
She is collaborating with Professor Anthony Chalmers, a clinical oncologist from the University of Glasgow, who leads clinical trials testing different combinations of radiotherapies and drugs in brain tumours and other cancers.
Adding to this expertise, the team also includes Dr Spencer Collis and Mr Ola Rominiyi, who have extensive expertise in glioblastoma biology, the development of patient-derived models of glioma, and the RNA sequencing analysis that will complement this research.
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:
