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Targeting DNA repair protein for the treatment of glioblastoma

Scientists at the University of Leeds have discovered that targeting a protein that helps cancer cells repair their DNA could lead to a new treatment for the highly aggressive brain tumour, glioblastoma (GBM).

Glioblastoma remains the most common high grade brain tumour found in adults, with limited effective treatments available for patients. Due to the complex nature of brain tumours, more specific and personalised treatments are needed.

Previous research has suggested that a specialised group of glioblastoma cells, called glioblastoma stem cells (GSCs), have the ability to give rise to duplicate copies of themselves. These copies have been shown to be resistant to radiotherapy, making it difficult to kill these cells.

The researchers at Leeds found that the GSCs have high levels of a protein called RAD51. RAD51 helps cancer cells repair the damage that radiotherapy causes to their DNA, allowing them to bounce back after treatment and enabling continued growth of the tumour.

The exact mechanism by which RAD51 becomes increased in cells that survive radiotherapy is not yet known, but our study provides strong evidence that this is the right protein to target in the treatment of this aggressive brain cancer“, says Professor Susan Short, lead author of the study.

Building upon their findings about RAD51, the team targeted this protein using small-molecule inhibitors to reverse these effects in animal models. Their data demonstrates inhibiting RAD51 is an effective means of sensitising GSCs to radiotherapy.

Improving the outcomes for glioma patients by adding drugs to increase radiation sensitivity have been the subject of much research, but there has not been much success in doing so. Whilst the inhibitors used in this study are not yet suitable for clinical trials, this important research funded by Cancer Research UK provides evidence that drugs that target RAD51 show effectiveness in helping to remove the tumour.

The next step will be to develop clinically suitable drugs that are safe and effective in larger studies with people, with the aim of moving these drugs from bench to bedside in the future.

Read more about this research.

Find out more about the research we fund at the Leeds Centre for Translational Neuro-Oncology.

(Credit: CRUK, Professor Susan Short at University of Leeds)