Lead investigator: Prof Deb Tweddle, Newcastle University
Funded by The Little Princess Trust and administered by CCLG
Funded December 2017
Award: £99.956.80
Neuroblastoma is the commonest paediatric solid tumour outside the central nervous system with around 100 new cases per year in the UK. Around half of all cases have ‘high-risk’ neuroblastoma, which despite many different types of treatment recurs (comes back) in over 50% of cases and is then incurable.
New treatments and a better understanding of the biology of relapsed neuroblastoma are needed before survival can significantly improve.
The team have been studying the genetics of neuroblastoma tumours from the same patient at initial diagnosis and at relapse using a technique called ‘whole exome sequencing’ and observed that several genes are recurrently mutated at relapse but not diagnosis.
The team thinks that the genes that are mutated at relapse but not diagnosis can be developed as targets for new therapies for neuroblastoma.
This study will determine if genes identified as mutated at relapse are also mutated at very low levels at diagnosis by “deep” sequencing of selected diagnostic neuroblastoma tumours. It will then measure the levels of proteins produced by these genes in neuroblastoma tumours with and without the gene mutation.
The team will then try to gain an understanding of the function of these genes and examine how they affect cell function and survival.
Ultimately the aim of the study is to identify whether some of these genes have the potential to be developed as targets for new anti-cancer therapies. If this is the case, the Newcastle University Northern Institute for Cancer Research drug discovery programme will select the most promising new candidate genes to develop further to treat neuroblastoma and other malignancies dependent on these genes and pathways within the next 2-5 years.