Sheffield researchers use pioneering technology to explore new treatments for fast-growing brain tumours

The city’s Teaching Hospitals NHS Foundation Trust is set to play a leading role in a pioneering new University of Sheffield research project, funded by The Brain Tumour Charity, which aims to develop new treatments for glioblastoma, a fast-growing and aggressive form of cancer.

Led by Dr Ola Rominiyi, Speciality Registrar in Neurosurgery, the cutting-edge research aims to exploit the ability of glioma cells, or cells found in the brain, to repair their DNA and survive treatment.

Glioblastoma is a rare, but devastating form of brain cancer, affecting 3,000 patients in the UK each year, with patients typically surviving 12-15 months after diagnosis. There is an urgent need for new treatments as survival rates have improved very little over the last few decades.

Dr Rominiyi is investigating tens-of-thousands of individual cells taken from tumour samples and diseased surrounding tissue removed from patients during surgery to see how the cells associated with a tumour behave.

The standard treatment for glioblastoma is surgery, where surgeons remove as much of the tumour as possible, followed by a combination of chemotherapy and radiotherapy. Both chemotherapy and radiotherapy are used to damage the DNA in cells, causing them to die. However, if cells can repair damaged DNA they can also survive and multiply – which makes the tumour harder to treat, and ultimately leads to the cancer returning.

The research aims to explore why some cells from different locations within the same tumour can withstand chemotherapy and radiotherapy better than others.

Researchers also hope that developing a cell-by-cell understanding of DNA repair mechanisms will improve the success of treatment and extend the lives of those living with a glioblastoma.

As well as investigating cells within the tumour, the team will also use cells that invade nearby brain tissue and are impossible to fully remove during surgery.

New ways to treat glioblastoma can then be designed which will prevent DNA repair in each of the different routes tumour cells would use.

Dr Rominiyi said: “Unfortunately, in fast-growing brain tumours, large differences in DNA repair within the same tumour present a major roadblock to improving patient survival. Our plan is to therefore map the different cells using a single cell-by-cell approach.

“We hope that by understanding the different cells within a tumour, as well as the cells which spread to nearby brain tissue, we can find ways to effectively switch off DNA repair in the cells, which will help to re-route the cancerous cells and improve patient outcomes and survival.

“Our close partnership between researchers at Sheffield Teaching Hospitals and The University of Sheffield will be key to the successful delivery of this research.

"This partnership enables us to provide opportunities for patients undergoing surgery in Sheffield to donate some of their brain tumour to support laboratory research developing more effective treatments for the future, and we would like to send our heartfelt thanks to our patients for the phenomenal contributions they continue to make to research."

Dr David Jenkinson, Chief Scientific Officer at The Brain Tumour Charity, which helped fund the project, said: “This project takes an innovative approach to finding new treatments for glioblastoma by mapping the different DNA repair mechanisms in different cells within the same tumour.

"Glioblastoma tumours are notoriously difficult to treat and there have been no significant treatment breakthroughs since temozolomide was approved in 2007.

"There is an urgent need for new, kinder treatments to improve lives for those with this devastating diagnosis.

"We are very excited about this project and look forward to following and sharing its success in the future.”

The work will be supported by Dr Spencer Collis, Reader in Genome Stability at the University of Sheffield, and be undertaken in collaboration with world-leading single-cell sequencing researchers in the US and Israel.

Patients undergoing brain tumour surgery at Sheffield Teaching Hospitals NHS Foundation Trust will be given the opportunity to donate tissue which would already have been taken during surgery as part of the removal of their glioblastoma.