Arginine deprivation alters microglia polarity and synergiseswith radiation to eradicate non arginine auxotrophicglioblastoma tumors (2022)
Scientists at the Brain Tumour Research Centre at Imperial College London have found that a drug which depletes the amino acid arginine made glioblastoma (GBM) tumours much more susceptible to radiotherapy, with the research paper being published in the Journal of Clinical Investigation.
Arginine, an amino acid used in the production of proteins, 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% of GBM tumours can make arginine, 30% cannot. 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 from access to arginine. The team is also exploring the potential for using ADI-PEG20 in the 30% of tumours that are not able to make arginine. If successful, this would mean that all GBM patients could be treated with arginine depletion.
Dr Nel Syed, from the Imperial team who is lead author of the paper 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.”