Understanding what the red flags are in aggressive neuroblastoma to improve and develop treatments

Neuroblastoma is the most common type of cancer seen in babies and unfortunately, is also one of the hardest to cure. Why and how childhood neuroblastoma develops is key research priority. What we do know is, unlike most adult cancers, childhood neuroblastoma has very few changes in DNA, the instructions that tell our cells how to behave and how to make proteins that are essential for survival. Instead, the cancer seems to be driven by ‘epigenetic’ changes, which affect how DNA is read and interpreted. Epigenetic changes have been shown to alter the behaviour of cancer and can make it more aggressive or resistant to treatment.

Professor Suzanne Turner and Dr Perla Pucci at the University of Cambridge want to find out more about how understanding epigenetic changes could improve treatment for children with neuroblastoma. In this project, they have two aims – to see whether the proteins which cause epigenetic changes could be stopped with medicines, and to find out which changes can be linked to how the cancer behaves.

If the researchers can show which epigenetic alterations are seen when tumour cells become resistant to treatment, or alter their growth to become more or less aggressive, they could be used as ‘biomarkers’ or red flags. If these changes can be picked up in a blood test, for example if the cancer cells release pieces of changed DNA into the bloodstream, doctors could use these biomarkers to help decide what treatments to give.

Professor Turner and Dr Pucci will assess patient tumours for the presence of epigenetic changes in order to develop a test to see if those same changes can be seen in the blood. If they can, the team will then assess whether the changes can be linked to specific clinical factors such as how a patient responds to treatment or whether they develop resistance to treatment.

At the same time, the team will screen hundreds of different drugs that could affect the epigenetic change-causing proteins to see if they can identify a new type of treatment for neuroblastoma. The drugs will be tested on lab-grown neuroblastoma cells and models, which will enable a more accurate demonstration of which drugs would be both safe and effective. Ultimately, the researchers hope to have developed a blood test to monitor how children respond to treatment and determine how aggressive their tumours are as well as having identified new drugs for further development.