Glioblastoma is a devastating brain tumour that kills three quarters of patients within a year of diagnosis. Current treatments can prolong survival but are not curative.
In this project, Dr Brooks will investigate a specific type of glioblastoma cells, called ‘polyploid cells’, which contain extra sets of DNA as a result of the radiotherapy used to treat glioblastoma. Her team will also test potential treatments to show whether targeting polyploid cells can improve treatment and lower the chances of the tumour coming back.
Glioblastoma is the most aggressive form of brain cancer. Each year, more than 12,000 people in the UK are diagnosed with a brain tumour, and glioblastoma accounts for approximately 20% of these cases. It is also the leading cause of cancer-related death in people under 40. Current treatments, which include surgery, chemotherapy, and radiotherapy, may slow the disease for a time, but nearly all glioblastomas come back. Survival rates remain low: only a quarter of patients survive more than a year from diagnosis, and only 5% survive five years.
One of the main reasons that glioblastoma is so hard to treat is that the cancer adapts. Even after high-dose radiotherapy, a small number of tumour cells can survive, recover, and regrow the tumour. Dr Brooks and her team have discovered that radiation causes some glioblastoma cells to become ‘polyploid’, meaning that they contain extra sets of DNA. These polyploid cells may be a hidden driver of recurrence, and there are currently no treatments that specifically target them.
This project aims to change that by uncovering how these polyploid cells survive and how to stop them.
Dr Brooks and her team recently discovered that radiotherapy causes a dramatic increase in polyploid tumour cells in glioblastoma. These cells contain extra copies of their DNA, which can make them more adaptable to stress. Rather than dying after treatment, the polypoid cells survive, re-enter the cell cycle, and go on to produce new tumour cells. This suggests that polyploid cells may play a major role in how glioblastoma comes back after treatment, so this project will investigate how to target and eliminate these polyploid tumour cells.
The team will begin by testing a shortlist of genes that their previous work suggests are essential for the survival of these cells. They will switch off these genes in tumour cells grown in the lab and use single-cell techniques to see how this changes the way in which polyploid tumour cells respond to radiation. Specifically, whether these cells die.
Next, the team will generate videos of individual tumour cells over time. This will allow the team to watch how polyploid cells behave after radiation and to see how blocking key survival pathways affects their fate. By identifying exactly when and how these cells become vulnerable, the team hope to pinpoint the best way to target them.
Finally, Dr Brooks and her team will test promising treatments on tiny “mini brain tumours” grown in the lab from patients’ own tumour cells. These 3D models behave much like real tumours, helping to show whether targeting polyploid cells can improve treatment and lower the chance of the cancer coming back.
This project will help us understand why glioblastoma is so challenging to treat and why some cells escape therapy. By uncovering how these resistant cells survive and identifying their weaknesses, the team aim to find ways to eliminate them. Doing so could unlock the full potential of existing treatments, reduce relapses, and spare people repeated rounds of therapy. Ultimately, this research could improve the survival of people with brain tumours and ensure more patients benefit from the treatments already available.
Dr Lucy Brooks primarily studies how glioblastoma cells adapt to treatment and investigates new ways to make these cells more vulnerable to therapy.
Dr Brooks is joined on this project by: Dr Jamie Dean, who leads the Computational Radiation Biology group at UCL, and uses advanced imaging to track how cancer cells respond to radiotherapy and drug treatments over time; Dr Xiao Qin, who is based at Oxford’s Weatherall Institute of Molecular Medicine, and is an expert in high‑throughput cell analysis and will enable large-scale profiling of tumour cell states; and Professor Puneet Plaha, a consultant neurosurgeon at Oxford, who brings clinical expertise and access to fresh patient tumour tissue, ensuring the research is clinically relevant.
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