Scientists at the Brain Tumour Research Centre of Excellence at Imperial College London have identified a promising new way to help radiotherapy work better against glioblastoma, the most aggressive form of primary brain tumour in adults.
On average, 3,200 people are diagnosed with a glioblastoma each year in the UK. The main treatments are surgery, radiotherapy and chemotherapy, which have not change in decades. Survival rates remain exceptionally low with only 4% of patients surviving their diagnoses for five years or more.
Thanks to funding from Brain Tumour Research, Dr Nelofer Syed (pictured) and her team have been exploring the link between radiotherapy and ADIPEG 20, a metabolic treatment that depletes cells of arginine, a key nutrient that some tumour cells depend on.
Radiotherapy works by damaging the DNA inside tumour cells, and for many types of cancer it is an effective treatment, but glioblastoma is particularly resistant because it has powerful systems that enable the tumour to repair damage to its DNA. In their new research, published in Cell Death & Disease, Dr Syed’s team has revealed that ADIPEG-20 can weaken glioblastoma’s ability to repair itself after radiation, and as a result the cancerous cells accumulate more damage and are less able to survive treatment.
Crucially, the researchers showed for the first time that this effect is linked to changes in the way tumour cells control their genes, changing how some genes are switched on and off. This reduces the activity of key DNA repair genes, including PARP1 and LIG1. These genes usually help tumour cells recover after radiation, so turning them down makes radiotherapy much more effective.
The study also revealed how quickly this process takes place. Increased DNA damage was observed within minutes of treatment and peaked within an hour, highlighting how powerfully this approach can amplify the effects of radiotherapy.
Lead Researcher, Dr Syed said, “Our recent findings strengthen the case for using arginine deprivation with ADIPEG‑20 alongside existing treatments. They suggest that combining this approach with radiotherapy, or with other treatments that damage tumour DNA, could help overcome resistance and make tumours more responsive, which could lead to better outcomes for patients. Importantly, this research also suggests that treatments that have not previously worked in glioblastoma might become effective again when paired with arginine deprivation.”
The next step for the research team is to explore these combinations in more detail, including testing ADIPEG‑20 with a wider range of DNA‑damaging treatments to find the most effective options. By doing so, the team hopes to pave the way for new clinical approaches that bring together metabolic therapies, targeted treatments and radiotherapy in a more personalised way. You can read the full paper here.
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