Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Helen Bryant, University of Sheffield
Award: £196,341
Awarded December 2020
Neuroblastoma affects approximately 100 children per year in the UK.
It is thought to arise in the womb when a group of normal embryo cells called trunk neural crest (NC) become cancerous due to changes intheir DNA. One such change results in the presence of very high levels of a gene known as MYCN. This isc onsidered to cause the change or “transformation” of normal trunk NC cells to neuroblastoma.
Patients that have high levels of MYCN have less than 50% survival rates because efficient treatments don’t exist. Little is known about what MYCN does during these early stages of neuroblastoma development because accurate ways to study the process didn’t previously exist.
We have developed a way to study this process in the lab. We can grow human trunk NC cells in a petri dish and then convert them into cancerous cells by artificially raising their MYCN levels. This is new. It offers fresh opportunities to understand how neuroblastoma starts and develops. It also provides a novel way to investigate how to stop the growth of neuroblastoma cells.
Preliminary studies showed that the cells with MYCN grew faster and had DNA damage, which is important because changes in cell growth and damage to DNA are known to be important steps in the early stages of many cancers.
We have 4 aims, which will increase understanding and identify potential new therapies. Using our model we will:
- Determine the effect increasing MYCN levels has on embryo and tumour cell development.
- Focus on changes in cell growth and damage to DNA.
- Test whether the drugs currently used/proposed to treat neuroblastoma kill cells in our model system.
- Test a panel of more than 4500 drugs used for other diseases in our system and see which can cause cell death.