Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Zoe Walters, University of Southampton
Award: £204,883.92
Awarded December 2020
Neuroblastoma is one of the commonest childhood cancers with up to 100 children newly diagnosed every year in the UK. Over half of these children have ‘high risk’ disease, for which the long-term survival is less than 50%.
Treatment strategies for this group consist of high-dose chemotherapy, stem-cell transplantation and treatment with an antibody called anti-GD2 and retinoic acid, a drug that stops cancer cells from growing by forcing them to mature. However, despite this intensive treatment, in many of these patients the disease will recur and be resistant to further therapy. There is therefore an urgent need to find better treatments.
Recent research studies have shown that high levels of a protein called EZH2 prevents cancer cells from maturing into non-cancerous (benign) cells. This protein is present at high levels in neuroblastoma cells and is required by them for survival. As both retinoic acids and EZH2 drugs can make tumour cells benign, we propose that treating neuroblastoma cells with a combination of these drugs will be a more effective, less harmful treatment for this disease.
Through this proposed work we aim to prove this in the pre-clinical laboratory setting. We will test the EZH2 inhibitors in combination with retinoic acid and/or anti-GD2 in models of neuroblastoma to show whether this combination of drugs is more effective than the drugs individually. We will also aim to identify potential biomarkers, or markers in the blood, which will help identify whether the treatment is working when it is used in clinical trials in patients.