Scientists at the Brain Tumour Research Centre of Excellence at Imperial College London are studying brain tumour biology, with a focus on glioblastoma multiforme (GBM). They are investigating how tumour cells get their energy, and how existing drugs can be made more effective, and can enhance treatments.
Their work is so important as GBM is the most common high grade primary brain tumours in adults, accounting for 12-15% of all brain tumours, and it is the most aggressive form of adult brain tumour.
Survival rates, however, remain low with less than 5% of patients surviving five years. Surgery is the first option for the treatment of a GBM, usually followed by radiotherapy and chemotherapy. Little progress has been made towards providing better treatment options for patients diagnosed with this devastating condition over the last few decades. Novel approaches for the management of GBM are therefore an urgent and unmet clinical need.
Scientists at Imperial funded by the charity have now published exciting research findings, in the Journal of Clinical Investigation, which could improve the effectiveness of current treatment and lead to an advancement in disease management.
The research has focused on being able to improve the efficacy of radiotherapy. Using a drug, ADI-PEG20, in combination with this treatment led to a lasting response with extended disease-free survival with no significant toxicity.
How does the drug work?
The drug degrades arginine, an amino acid which is critical for the growth and survival of human cancers. In combination with treatment regimes, the results suggest that by reducing the supply of arginine, GBM tumours are much more susceptible to radiotherapy.
In addition, the drug appears to affect the body’s immune response to the cancer too; immune cells around the tumour were more likely to attack and remove tumour cells.
This is important as the tumour microenvironment tends to be pro-tumour and immunosuppressive enabling the GBM to evade the immune response. With the addition of ADI-PEG20, the immune cells became anti-tumour, actively recognising and attacking the cancer cells.
What could this mean for patients?
Whilst these studies were undertaken in the laboratory using preclinical models, the results are promising. Clearly the next step will be to explore the safety and effectiveness in humans by setting up a clinical trial – we’re pleased to report that data from the Imperial research has already helped inform a clinical trial in Taiwan where a small cohort is being enrolled to evaluate ADI-PEG 20’s efficacy in combination with radiotherapy and Temozolomide in patients with GBM. The trial is due for completion at the end of 2023.
The studies funded by Brain Tumour Research show that our researchers are improving the use of current treatments in combination to an effort to maximise the impact on brain cancer and stop or slow down the growth of GBM. Therefore, whilst we await alternative therapies to those already available, there is hope that modifying current, dual treatments can make a great difference in eliminating this tumour.
This research has provided useful insights into how the immune response to GBM can be altered positively to kill the cancer cells. More research is needed to further explore these findings for patient benefit. Brain Tumour Research is working to sustain the vital research at Imperial College to enable them to take these next steps.