Lead investigator: Dr Madhumita Dandapani, University of Nottingham
Funded by The Little Princess Trust and administered by CCLG
Funded July 2017
Award: £24,891.00
Brain tumours account for 25% of all childhood cancers. The significant improvement in cancer survival achieved across all childhood cancers has, however, not been seen for brain tumours. Some brain tumours such as diffuse intrinsic pontine glioma and atypical teratoid rhabdoid tumour still have poor prognoses.
Those cured are often left with a profound disability affecting their quality of life due to either the effects of the tumour itself or the damaging effects of treatment. Tumour recurrences are common with treatment options at recurrence becoming more limited with very poor outcomes.
There has been a dramatic increase in the understanding of the nature and biology of brain tumours in the last decade, through advances in high resolution genetic analyses. However, despite these advances, there is still a need to identify the alterations in these children’s brain tumours that can be targeted and so lead the way to developing new, more effective treatments with fewer toxicities.
Targeting amino acid metabolism is a novel approach to treating cancer. Arginine is an amino acid that plays a key role in cellular processes. Due to a fault, some tumour cells cannot produce arginine and rely on obtaining it from the blood (arginine auxotrophism or addiction). Therefore depletion of arginine from the blood may be exploited in order to treat cancer – so-called arginine depletion therapy.
Pilot data shows that arginine depletion therapy could prove effective for a wide range of childhood brain tumours.
We are in the process of developing a Phase II clinical trial in the UK to test a new drug, which depletes arginine in blood in the treatment of relapsed childhood cancers and cancers that are resistant to other treatments. However, the arginine pathway status of several cancers, particularly childhood brain tumours, is as yet unknown. Our pilot data (described above), in addition to that proposed in this application, will help determine which patients would benefit from arginine depletion therapy.
If found to be very effective, it could potentially reduce the need for current therapies, and actually reduce toxicities for patients in the short and long term.