New treatment could boost radiotherapy effectiveness for brain tumour patients

Tumour cells derived from a glioblastoma multiforme (GBM) tumour

A new treatment could significantly improve the effectiveness of radiotherapy for patients diagnosed with the deadliest form of brain tumour.

Researchers at Imperial College London found that a drug which depletes the amino acid arginine made glioblastoma (GBM) tumours more susceptible to radiotherapy. 

The new research, funded by the charity Brain Tumour Research, is published in the Journal of Clinical Investigation.

Targeting tumour growth

GBM is the most common type of primary high-grade brain tumour in adults and also the most aggressive and deadly. Less than one per cent of patients with GBM live for more than ten years and, for many, the prognosis is as little as 12 months.

Arginine is an amino acid used in the production of complex molecules called proteins, which conduct a vast range of functions within cells. Arginine is required by a variety of cancer cells, especially ones that are growing quickly, and therefore depriving tumours of this amino acid has been explored as a potential anti-cancer strategy in a variety of tumour types, including GBM.

Whilst 70 per cent of GBM tumours are able to make arginine, 30 per cent are not. In this study, the research team focused on the tumours that can make arginine by exposing them to a drug called ADI-PEG20. This drug degrades arginine and the aim was to deprive tumours of access to arginine. The team is also exploring the potential for using ADI-PEG20 in the 30 per cent of tumours that are not able to make arginine. If successful, this would mean that all GBM patients could be treated with arginine depletion. 

Radiotherapy boost

"We found our approach meant immune cells around the tumour were more likely to attack and remove tumour cells.” Dr Nel Syed Senior Research Fellow

Dr Nel Syed, who leads the team at Imperial's Brain Tumour Research Centre in the Department of Brain Sciences, said: “Arginine is a vital nutrient for tumour growth and our results show that reducing its supply makes tumours much more susceptible to radiotherapy."

"Removing arginine removes tumour immunosuppression and we found our approach meant immune cells around the tumour were more likely to attack and remove tumour cells.”

“Laboratory results showed that using the drug ADI-PEG20 in combination with radiotherapy, led to a durable response with extended disease-free survival with no significant toxicity. The next steps are to explore the safety and effectiveness of using this in humans by setting up a new clinical trial.”

Hugh Adams, Head of Stakeholder Relations at Brain Tumour Research, said: “This is a significant and exciting finding. There is an urgent need for novel approaches to treat GBM which, in the majority of cases, is fatal. There have been no improvements to treatment options for this type of tumour in two decades. 

“Despite the promise of new targeted approaches in cancer treatment, the standard of care for patients with GBM remains unchanged - surgical resection followed by radiotherapy and chemotherapy.”

This article has been adapted from a press release by Brain Tumour Research

'Arginine deprivation alters microglia polarity and synergises with radiation to eradicate non arginine auxotrophic glioblastoma tumors' by Nabil Hajji et al. is published in the Journal of Clinical Investigation.

Image credit: Highly invasive human paediatric brain tumour derived cells. Valeria Molinari, Louise Howell, Maria Vinci, Katy Taylor and Chris Jones, Institute of Cancer Research. (CC BY-NC 4.0)