Scientists at the Brain Tumour Research Centre of Excellence at the University of Nottingham have identified promising new ways in the laboratory to target glioblastoma, offering fresh hope for treatments that could help stop this devastating disease from returning after surgery.
Led by Dr Phoebe McCrorie, Senior Research Fellow, the study focused on tumour cells found at the edge of glioblastoma tumours – known as the invasive edge. These cells are particularly important because they often remain behind after surgery and are thought to drive tumour regrowth.
Glioblastoma is the most common and aggressive type of primary brain tumour in adults. Despite decades of research, surgery, radiotherapy and chemotherapy remain the standard of care, and no new treatments have been approved for patients in more than 20 years. Survival remains devastatingly low, with just 4% of patients living five years or more after diagnosis.
Published in Neuro-Oncology Advances, the research compared proteins found in patient-derived glioblastoma cells with those in healthy brain cells. The aim was to identify targets that could be attacked by future therapies while minimising damage to healthy tissue.
By focusing on proteins found on the surface (membrane) of tumour cells, which are more accessible to drugs, the team identified several promising targets, including LOXL1, A2M and SH3KBP1. These are all proteins involved in the normal function of cells, but previous studies have linked these proteins to tumour growth, spread and poorer patient outcomes.
The researchers then used computer-based screening to search for existing medicines that could target these proteins. Their findings suggest that two approved drugs, nilotinib (used to treat leukaemia) and darifenacin (used in the treatment of overactive bladder), could be worth investigating further. This approach, known as drug repurposing, has the potential to accelerate the development of new treatments by building on medicines that have already undergone safety testing and therefore reducing the steps required to reach a clinical trial in patients.
While the findings are still at an early stage, using cells in the laboratory, they represent an important step towards developing treatments that can target the cells left behind after surgery. Further research will be needed to understand exactly how the drugs work, validate the targets in patient samples and determine whether the approach could ultimately benefit patients.
Dr McCrorie, senior author of the study, said: "Glioblastoma is incredibly difficult to treat because tumour cells are so diverse and can spread into surrounding brain tissue. We wanted to identify proteins that are consistently present in those invasive cells left behind after surgery and which could potentially be targeted with therapies.
"We found 18 membrane proteins that were increased across multiple patient-derived cell lines and identified existing drugs that may be able to target some of them. While there is still a great deal of work to do, these findings provide a valuable starting point for developing more targeted approaches against glioblastoma recurrence."
Dr Karen Noble, Director of Research and Policy at Brain Tumour Research, said: ”Dr McCrorie's findings add to the growing body of research aimed at tackling one of the greatest challenges in glioblastoma treatment: preventing the tumour from returning after surgery. Although further validation is needed, studies like this are helping to build the foundations for more precise and effective therapies.
“By investing in Centres of Excellence and supporting researchers such as Phoebe, we are accelerating progress towards finding better treatments for brain tumour patients."
The researchers believe the discovery pipeline developed during the study could also be applied to other adult and paediatric brain tumours, potentially helping identify new treatment opportunities across a wider range of diseases.
Dr McCrorie is a Senior Research Fellow at the Brain Tumour Research Centre of Excellence at the University of Nottingham where researchers are using advanced brain imaging, genomic sequencing and AI to better predict glioblastoma recurrence and help guide personalised treatment for patients.
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