Dr Helen Bryant, University of Sheffield
Neuroblastoma has a ‘high-risk’ form that has a poor prognosis despite intensive treatment. Some high-risk neuroblastomas have extra copies of the MYCN gene and Dr Helen Bryant wants to clarify the role of this gene. She will be testing the effects of a new drug used against ovarian cancer, as well as other similar drugs, on MYCN neuroblastoma. This will give a better understanding of this devastating tumour and potentially some new treatments in the short- to medium- term.
Amount of grant: £49,300 | Date of award: July 2016
Neuroblastoma is a type of children’s cancer that arises in specialised nerve cells, usually within the abdomen. It is one of the most common cancers seen in children, with around 100 new cases every year in the UK.
Nearly half of all children diagnosed with neuroblastoma have ‘high-risk’ disease, with a poor prognosis. This is often when their cancer has extra copies of a gene called MYCN. The treatment given to these children includes intensive chemotherapy, radiotherapy and surgery. Despite these efforts, more than half of children with high-risk neuroblastoma will die.
Previous research has given us a good understanding of many of the functions of MYCN but we still know little about the effect of MYCN on the way that DNA repairs itself. Every cell in the human body, including in cancer, contains DNA. This is the blueprint for life and cells cannot survive without it. DNA is constantly being damaged and our bodies have developed efficient ways to repair it.
We know that in certain types of cancer DNA is not repaired properly. Dr Bryant believes that this may be the case in neuroblastoma, possibly due to MYCN. She believes that this could be the key to the development of more effective and less toxic treatments for young neuroblastoma patients.
These kinds of cancers can be killed by certain drugs that also affect the way in which DNA is repaired. The most famous example of this type of drug is called Olaparib. This drug, which was developed in Dr Bryant’s laboratory, has been recently approved for women with ovarian cancer and is already saving lives.
The team has new evidence that Olaparib may be effective in neuroblastoma, particularly in MYCN neuroblastoma. They want to analyse the effects of Olaparib in neuroblastoma cells in the laboratory and examine how it kills them. They will also assess the effects of other similar drugs and whether they work better with the chemotherapy and radiation treatment that we already use. Lastly, they want to determine how MYCN makes neuroblastoma cells sensitive to these types of drugs and specifically its effect on DNA repair.
About the research team
This is a research team with a very strong track record in studies of DNA damage repair in other cancers.
External reviewerAn experienced team of researchers at the University of Sheffield will be involved in this project, headed up by Dr Helen Bryant.
Dr Bryant has more than twenty years’ experience of researching cancer and her work has led to a number of important discoveries. In particular, her work on breast cancer has led to new and more effective treatments for this disease.
Dr David King is a children’s doctor employed by the University of Sheffield as a clinical lecturer in paediatrics; this project will form the basis of his PhD.
Dr Daniel Yeomanson is a paediatric oncologist at Sheffield Children’s Hospital who will bring his clinical expertise to ensure that children with neuroblastoma benefit from this work as soon as possible.
This mix of basic scientists and clinicians is the ideal way to explore and translate findings from the laboratory bench to a direct benefit for a child with cancer. The required techniques are already running in Dr Bryant’s laboratory and Dr Bryant has the expertise to see this project through to a successful conclusion.
What difference will this project make?
This project has the potential to provide significant benefits to young patients. Neuroblastoma is responsible for up to 15 per cent of childhood cancer deaths and current treatment has many short- and long-term side-effects. New treatments are urgently needed.
Most of the drugs being tested here are already in clinical development or have been approved for other types of cancer in adults. If the team can generate evidence supporting the use of these drugs in neuroblastoma, it should therefore be relatively straightforward to test them in the setting of a clinical trial.
The project will also give insights into how neuroblastoma cells are cancerous and more broadly, about how cancer genes affect the way in which DNA is repaired. This may lead to new treatments for other types of cancer in the future.
Importantly, this funding will also provide key research training for Dr David King. It is only through investment in a new generation of academic paediatric oncologists that we can continue to make progress towards curing all childhood cancers.
Read more: About neuroblastoma | Other neuroblastoma projects