Medulloblastoma (MB) is the most common malignant brain tumour in children. This project is looking at a protein called p73, which plays a central role in the development of the central nervous system and in metabolism. We hope that this protein will help us to identify new ways of treating MB that are more effective and have fewer side effects than surgery and radio/chemotherapy.
This research project on medulloblastoma has been successfully completed. Your donations allow us to fund ground-breaking research that can improve treatments given to children with cancer. Thank you. Your help allows us to continue to find ways to drive up the chances of survival for children with cancer and reduce the toxic side effects that can affect the rest of their lives.
Metabolic analysis of the tumour suppressor protein p73 in medulloblastoma
Queen Mary University of London
London E1 2AT
1 September 2014
Medulloblastoma (MB) is the most common malignant brain tumour in children. Scientists are working hard to increase the current five-year survival rate of 60-70per cent, and improve the quality of life for survivors. Although the surgery, radio and chemotherapy can be effective, they can also have significant side effects and children who survive can experience disabilities later on. We’re looking for more targeted treatments that attack the tumour without causing more damage to the brain.
We now know that metabolic adaptation is a hallmark of cancer. Rapidly growing cancer cells adapt their metabolism by increasing nutrient uptake and energy production. Stopping them doing this will help stop the growth.
The protein p53 is a known as a “tumor suppressor gene” because it stops tumours forming. A p53-family member, the protein p73 plays a key role in the development of the central nervous system and in the regulation of metabolism.
Dr Niklison-Chirou is studying how p73 is involved in MB and in particular its role in metabolic adaptation of these tumours. Her final goal is to understand whether targeting p73 could help treat them.
Through her research Dr Niklison-Chirou discovered that aggressive medulloblastomas that express the p73 protein are addicted to an amino acid called glutamine. Glutamine is common in our diets and found in foods such as beef, chicken, fish, dairy products, eggs, wheat and vegetables such as beans, beetroot, cabbage, spinach and carrots.
This addiction means that glutamine starvation or glutamine inhibitors can restrict the growth of aggressive Medullablastoma (MBs) and this was demonstrated in MB tumours in preclinical models. Additionally, Dr Niklison-Chirou found that a glutamine restricted diet improved the effect of chemotherapy treatment for MB in these preclinical models.
Understanding how p73 changes the metabolism in MB cells, has the potential to uncover key factors allowing cancer cells to adapt and survive under metabolic stresses such as low oxygen environment and nutrient starvation and this research will help to lay the basis for the discovery of new disease characteristics for drug targeting.
Dr Niklison-Chirou was awarded a Paul O’Gorman Fellowship through Children with Cancer UK, a personal award intended to develop a researcher’s career in childhood cancer. Following the end of this award, Dr Niklison-Chirou will take up a lecturer post in University of Bath, where she will continue her research into medulloblastoma tumours.
Dr Niklison-Chirou’ will carry out her research in the Blizard Institute at Barts and The London School of Medicine, Queen Mary University of London, a highly dynamic and international research environment. She has expertise in molecular mechanisms of cancer metabolism combined with the unique pre-clinical and translational brain tumour knowledge at the Blizard Institute.
She’ll interact with Silvia Marino, a world-renowned expert in epigenetic regulation in brain tumours with expertise in translational neuro-oncology research. Dr Maria has also established essential collaborations with Dr Marc Remke, Prof. Steve Clifford and Dr Tom Jacques for access to DNA dataset and RNASeq dataset on human MB and MB primary cells respectively.