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Understanding the margin zone in brain cancer

Project details

Mr Ryan Mathew
University of Leeds
Research area
Brain tumours
Funding type
Project grant
Awarded in
September 2020


Despite huge progress in the treatment of many cancers, the prognosis for those with brain cancer remains bleak. Even with the best available treatment, patients with the most aggressive brain tumours live for only 12 to 15 months.

Treatment for malignant brain tumours often fails because cancer cells remain in the brain after surgery. These cells resist being killed by radiation and chemotherapy, and ultimately give rise to new tumours. Neurosurgeon Ryan Mathew brings together a team of neurosurgeons and biologists from across three universities to tackle this problem.

Following rigorous assessment as part of our competitive grant round, this project was recommended for its strong potential to advance knowledge of the cancer cells remaining in the ‘margin zone’ and the development of new experimental systems that will underpin future research. The work is based on a solid body of high-quality preliminary data and presented by an outstanding, multi-institutional collaborative team led by an early career academic neurosurgeon.


Glioblastoma is the most common primary brain cancer in adults, with around 2,500 cases diagnosed every year in the UK.

It is an aggressive, invasive tumour that grows and spreads quickly, and infiltrates the brain.

The current treatment strategy includes surgery to remove as much tumour as possible, followed by radiotherapy and chemotherapy to destroy remaining tumour. This prolongs survival but is not curative. Only a quarter of patients survive more than a year from diagnosis.

The need for better understanding and new treatments is urgent.

Read more: About brain tumours

New tools to understand the margin zone

One of the main barriers to successful treatment of brain cancer is that the tumours do not have a clean boundary, they grow into the surrounding healthy brain. This makes surgical removal extremely challenging and it means that, whilst surgery is often effective at removing the majority of the brain cancer ‘lump’, cancer cells are almost always left behind in a ‘margin zone’ that comprises both cancer cells and healthy brain tissue.

Unlike surgery for cancers in other parts of the body, brain surgeons cannot take out extra tissue to be sure of getting all the cancer cells - the risk of damaging vital brain tissue is too high. And so these remaining cells are targeted with radiation and chemotherapy. Despite this, the tumours almost always regrow.

Despite the fact that it is the cells in the margin zone that cause relapse, very little is known about the way that these cells behave as most brain cancer research focuses on the main lump. Understanding the difference between the cells in the main lump and those in the margin zone is key to finding new ways to prevent relapse.

In this project, the team will recreate human brain cancer surgery in mice and rats. This will enable them to study the cancer cells in the margin zone, work on better ways to eliminate these cells, and test treatments that might be given at the time of surgery.

Read our policy on the use of animals in medical research


Animal models of brain cancer are a crucial resource in the study of these tumours, to take forward our understanding of how tumours develop and grow in a living system, and how they respond to treatment.

Although brain cancer animal models exist in the UK, there are none that recreate the surgery that patients undergo, none in which cells in the margin zone can be studied and treated in live conditions, and none in which the tumour regrows.

Thus, the work being carried out here will have a significant impact on brain cancer research in the UK because not only will it deliver new knowledge about cells in the margin zone, but the team will share their models with other researchers, accelerating efforts towards the development of effective treatments.

“This is an excellent proposal. Even if it delivers half of what it promises, it will deliver very high value. Mr Mathew has built an excellent collaborative grouping here and this proposal is pivotal to their growth.” Reviewer

About the research team

The project team combines a unique blend of expertise in brain cancer, cell science and animal modelling. Ryan Mathew (Leeds) and Stuart Smith (Nottingham) are Consultant Neurosurgeons and brain cancer researchers who perform brain tumour surgeries weekly, have finely developed technical skills and obtained PhDs in lab-based brain cancer science.

Dr Heiko Wurdak (Leeds) and Dr Ruman Rahman (Nottingham) are brain cancer scientists with extensive experience studying the behaviour of cancer cells. Dr Peter O’Toole (York) is an expert in ‘cell mapping’ technology and Alison Ritchie (Nottingham) is an expert in developing animal systems for the study of human disease.

“This is an outstanding team composed of investigators with strong and complementary knowledge and expertise.”
“The teams are all leaders in their fields and Mr Mathew is an emerging talent as an academic neurosurgeon whose work is truly biologically translational – something which is to be valued and actively supported.”

Related projects

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.

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