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 promising new avenue of research, focused on the importance of cholesterol on the growth and survival of glioblastoma cells.
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 not improved outcomes for patients and glioblastoma remains incurable. Only a quarter of patients survive more than a year from diagnosis, and just 5% survive five years.
The current treatment strategy includes surgery to ‘debulk’ the tumour, followed by radiotherapy and chemotherapy to destroy remaining tumour. Whilst this prolongs survival, the tumour always grows back and the recurrent tumours display resistance to further treatment.
This treatment resistance is due 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 essential.
Cholesterol is a fatty substance needed by our bodies, but damaging if present at a high level. Recent research has revealed that it plays a role in glioblastoma; glioblastoma cells have unusually high levels of cholesterol and rely on it to survive. When they have too much cholesterol, they grow faster and become more resistant to chemotherapy and radiation.
In laboratory studies, Dr Gomez-Roman and others have found that blocking the movement of cholesterol within cells is very effective at killing them.
They found 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. They also found that genes involved in cholesterol movement are more active in GSCs compared to other glioblastoma cells, suggesting a link between cholesterol movement and tumour growth.
In this project, Dr Gomez-Roman will study the storage and movement of cholesterol in glioblastoma and normal brain cells. She will investigate how the genes and proteins involved in cholesterol movement affect the formation and growth of glioblastoma tumours, and see how blocking them affects the behaviour of the tumours - both alone and in combination with radiation and chemotherapy.
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. 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 genetic analysis that will complement this research.
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