Therapeutic and preventative strategies for children with high-risk neuroblastoma: targeting high fat diet-related metabolism.

Amongst the most aggressive and treatment-refractory childhood malignancies is high-risk neuroblastoma (NB). Whilst the survival of high-risk NB patients has improved over time, relapse rates in high-risk NB remain high at 50-60% with 5-year survival rates being less than 50% for these patients.

Considerable evidence suggests that NB begins in embryonal neuroblasts indicating an aetiological relationship between NB tumorigenesis and embryonal environmental factors. Some studies have suggested that maternal obesity and high birth weight  are risk factors for childhood cancer. 

We found that neuroblastoma driven by the MYCN proto-oncogene, originates from embryonal precancer cells persisting postnatally due to the loss of the normal death response. We discovered a drug which specifically restored the death response to these persistent embryo cells without affecting normal cells, and reduced tumour initiation in mouse models of child cancer. This drug appears to work by blocking cholesterol metabolism in the embryonal precancer cells. This research project will investigate a mechanistic understanding of how high fat diet, maternal obesity and high birth weight contribute to the aetiology of childhood cancer initiation and development, and will enable development of effective agents for intervention during pregnancy or in early life that may reduce the incidence of childhood cancer.

Techniques and key outcomes /learnings:

The Higher Degree Research Candidate will master cutting edge cellular and molecular techniques to test hypotheses that high fat diet-induced maternal obesity and high birthweight accelerates NB initiation by activation of fatty acid metabolism, leading to suppression of anti-tumour immunity, some techniques will include:

1. Therapeutic targets and drug identifications.
2. Molecular techniques using gene overexpression, knockdown and knockout.
3. Developing cancer prevention strategies. 
4. Experience in working with transgenic and xenograft animal models.

How to Apply

Express your interest by emailing Associate Professor Belamy Cheung at bcheung@unsw.edu.au. Include a copy of your CV and your academic transcript(s).