Pre-emptive targeted therapy to optimise high-risk neuroblastoma treatment

Despite intensive and prolonged treatment, half of all children diagnosed with high-risk neuroblastoma either do not respond, or subsequently relapse. There are no curative therapies for these patients. Current approaches are clearly inadequate for these children, and experimental therapies are being introduced too late. This study aims to change this paradigm through comprehensive pre-clinical evidence supporting earlier intervention with targeted agents.

Children diagnosed with high-risk neuroblastoma (HR-NB) undergo intensive and prolonged treatment with conventional high-dose, multi-agent chemotherapy, surgery, radiation therapy and immunotherapy. However, nearly 50% have refractory disease or experience relapse, and despite numerous early phase clinical trials, their outcomes remain especially poor, with survival <10%. Recurrent mutations in a restricted number of survival pathways occur in >50% relapsed or refractory HR-NB, suggesting that activation of these pathways allows tumour cells to persist through conventional chemotherapy. We propose that combination treatment targeting these pathways, would be more effective than conventional therapy at diagnosis.

This project will generate high-quality pre-clinical evidence to support the early introduction of targeted agents into frontline rather than relapse HR-NB clinical trials. This paradigm shift is essential to support intervention with new agents where they are more likely to be effective.

How to Apply

Express your interest in this project by emailing Dr Jamie Fletcher at JFletcher@ccia.unsw.edu.au. Include a copy of your CV and your academic transcript(s).