Projects we fund

Overview

Neuroblastoma is the second most common solid tumour in children, and the five-year survival rates for high risk types of the disease is only 50%. Many high-risk neuroblastoma cases show amplification of what scientists call the MYCN oncogene. Mutation or amplification of the gene called Anaplastic Lymphoma Kinase (ALK) also confers a particularly poor prognosis, and is this is most commonly seen in children who have already had treatment but have relapsed. Doctors have found evidence to suggest that some relapsed tumours, having been treated with chemotherapy, are more likely to mutate into new subclones of tumours – and these mutations make them harder to treat again. In this project, Dr Calton is looking at how chemotherapy resistance develops in these tumours – investigating the mutations which happen in relapsed tumours in order to identify which genes are suitable for therapeutic targeting effective in the complex cancers which affect children who have been treated but have relapsed.

Potential impact

This project will directly impact the testing of new molecular therapies for neuroblastoma. By ensuring that the model environment Dr Calton studies more closely represents advanced tumours, she expects to increase the ability of neuroblastoma researchers to transfer new drug discoveries into tests in hospitals, and give more critically-ill children a better chance of survival. Metastasis, the spread of a tumour to other parts of the body – in the case of neuroblastoma, particularly to bone and bone marrow – affects 40% of all children at diagnosis, and is responsible for the majority of childhood deaths from neuroblastoma. Therapy which can effectively limit this would be major step forward, and this project will advance our understanding of this aspect of the disease. The project will also enable scientists to suggest new drug targets for relapsed and refractory neuroblastoma. We will identify the specific mutation events in pre-treated tumours, and explore their effects on tumour aggression and metastasis, and by examining what makes them resistant to chemotherapy, suggest combinations of targeted drugs to overcome this resistance. These suggestions can then be effectively translated into new drug candidates to give more children a chance to survive this disease.