Finding a Cure
There are two ways to find a cure for neuroblastoma. The first is to conduct research into the disease in order to find better treatment. The second is to explore through clinical trials how effective existing and new combinations of treatment are in improving recovery from the disease and survival.
Just click on any of the links below to go directly to more information on that topic.
- Research Approach
- Research in Progress
- New Research
- Clinical Trials
- International Co-operation
- International Travel Bursary
Research Approach
Over the past decade or so the Society has single-handedly funded about £2.5 million dedicated neuroblastoma research at specialist centres throughout the UK. A research study is only supported if it has passed a rigorous scrutiny by two or three experts chosen for their specialist knowledge of the proposed research area and then been evaluated and recommended by the Society's Scientific Advisory Board of leading neuroblastoma researchers and clinicians. Grants are then awarded by Trustees in the light of that advice within the limits of funds available.
Normally research grants are awarded in alternate years in order that there are adequate funds available to support major in-depth studies over three years if appropriate. Currently the Society is supporting thirteen studies with grant awards exceeding £1.7 million.
Research in Progress
Dr. Sala, London Institute of Child Health (2002 award)
This study tests the hypothesis that abnormal B-MYB expression may cause neuroblastoma.
The function of B-MYB is essential for normal cell growth and development.
Other studies have shown that it can interfere with differentiation of neuroblastoma cells and reduce sensitivity to chemotherapy drugs, as well as modifying the activity of tumour and growth suppressor proteins in the cell.
A further grant was awarded in 2005 to extend this study for a further year.
Dr. C Redfearn, Newcastle University (2004 award)
This study explores whether novel agents like fenretinide (a synthetic version of vitamin A), used alone or in combination with conventional drugs will lead to substantial improvement in the prospects of children with high risk neuroblastoma.
Fenretinide has been found to improve the effect of chemotherapy drugs.
This study explores whether these effects are reproduced in a preclinical model and what the most effective treatment schedule would be.
Dr. G Flux, Royal Marsden NHS Trust / Institute of Cancer Research (2004 award)
Targeted mIBG (known as 'the magic bullet'), is widely used throughout Europe as part of the treatment for neuroblastoma.
At present patients are usually treated with a fixed amount of radioactivity, but it is known that how much radioactivity is taken up and retained by malignant tissue varies from patient to patient.
This study aims to develop methods needed to calculate the amount of energy deposited in tumour tissue.
This will provide the basis for tailoring treatment to individual patients, and will form the foundation for a European network for mIBG therapy.
This may in turn generate further European funding and collaboration.
Dr. S Lain, Dundee University (2006 award)
JJ91 is a novel compound less harmful to the cell than current chemotherapy drugs.
The aim of this study is to test its effectiveness on a pre-clinical model for neuroblastoma.
Dr. M Pule, London University (2006 award)
This study continues previous work on developing genetic engineered T-cells to treat relapsed neuroblastoma patients.
Prof. M White, Liverpool University (2006 award)
Neuroblastoma is effective in resisting current chemotherapy treatment designed to bring about cell death.
This project will track the processes that keep neuroblastoma cells alive and study how old, new and combination chemotherapeutic agents affect these processes.
Prof. N Rahman, Institute of Cancer Research (2006 award)
The aim of this study is to identify and characterise neuroblastoma susceptibility genes in order to understand the underlying mechanisms causing the disease.
Dr. R Mairs, Glasgow University (2006 award)
This study builds on earlier work that showed the effectiveness of combining mIBG and topotecan.
This combination will be evaluated with threee other cytotoxic drugs to see if effectiveness can be further improved.
New Research
On 17 June 2008 Trustees awarded research grants totalling nearly £700,000 to five research teams in UK universities and laboratories. The projects funded are:
Professor Susan Burchill, Leeds Institute of Molecular Medicine, St. James's University Hospital
Minimal disease in children with high-risk neuroblastoma.
The study aims to apply a new technique (QRT-PCR) to bone marrow and tumour samples from children with high-risk disease.
This technique is more sensitive than traditional methods, allowing detection of a single neuroblastoma cell.
This may provide a method to monitor the response of children to therapy, allowing doctors to identify children who may benefit from increased therapy and those for whom additional therapy may be unnecessary.
Dr Louis Chesler, Institute of Cancer Research, Royal Marsden Hospital
Development of Mycn-targeted drugs for the treatment of high-risk neuroblastoma.
The study aims to test a second generation of drugs known as PI3-kinase inhibitors.
These target the MYCN protein without damaging other tissues and cells, which is a major factor affecting how well a child copes with and responds to treatment.
Dr Diana Moss, University of Liverpool
Using lessons from embryonic neural development to disarm cancer stem cells in neuroblastoma.
The study will test if introducing neuroblastoma cells into an early embryonic environment reprogrammes them toward benign behaviour.
This approach takes its cue from the way that embryonic stem cells and melanoma cells change their 'normal' behaviour when transplanted to a different environment.
This would help determine ways to divert neuroblastoma cancer stem cells away from tumour formation and into benign and hence curable derivatives.
Dr Arturo Sala, University College of London Institute of Child Health
Re-activating ApoJ/clusterin expression as a novel therapeutic approach for neuroblastoma.
This study aims to understand the precise mechanism by which MYCN (a gene implicated in aggressive neuroblastoma) downregulates the
ApoJ/clusterin gene, and whether reactivating ApoJ/clusterin inhibits neuroblastoma development.
These so-called 'epigenetic' drugs are already approved for use in adults so success with the project could pave the way to their use for children with aggressive neuroblastomas.
Dr N Bown, Northern Genetics Service, Institute for Human Genetics, Newcastle upon Tyne
U.K. National Reference Centre for Neuroblastoma Biology.
This award will fund continuation for the next 3 years of an analysis service already used by hospitals for existing neuroblastoma cases.
It is a centre of excellence for assessing the biology of neuroblastoma tumours using fluorescent in situ hybridisation (FISH) and
multiplex ligation-dependent probe amplification (MLPA).
This award represents an exciting new departure for the Society as it provides support not only for research but also for clinical practice, and thus has a direct bearing on the current care of children with neuroblastoma.
It also supports UK participation in Europe-wide neuroblastoma biology research.
While the Society and its advisers consider that such services should be publicly funded as part of the NHS, they recognise the difficulties faced in securing such funding.
In addition to agreeing to fund the service for 3 years, the Society will require the team to actively seek longer-term sustainable funding and has offered to assist and support them in doing so.
Clinical Trials
Improvements in treatment of the disease have come through clinical trials. These ensure that the effects and outcomes of particular aspects of treatment are measured consistently and reliably over time, to see if they improve survival. Clinical trials may also involve the comparison of different treatments where it is not known whether one drug or procedure is more effective than another.
With the small number of children in the UK with the disease, trials had to run for many years to get statistically valid results. UK treatment centres now take part in European-wide trials that have a much larger number of children in them. This means that conclusions are reached more quickly for the benefit of all children.
Before any UK child is included in a clinical trial the treatment team will explain what the trial is aiming to achieve, and the risks and benefits of taking part in it. It will only be after the trial has been fully explained and the parent has had time to consider the matter that informed consent to entering the trial will be requested.
Survival of UK children with neuroblastoma has improved over the past 25 years, through effective clinical trials identifying better forms of treatment. Now 2/3rds of children can expect to survive 3 years after diagnosis, compared with one in five 20 years ago although, sadly, most of these children will subsequently relapse and die.
The Children’s Cancer and Leukaemia Group (CCLG) is a national professional body responsible for the organisation of the treatment and management of children with cancer in the UK. The Group's main remit is the coordination of national and international clinical trials, including biological studies. CCLG is working closely with CancerHelp UK, a free patient information service from Cancer Research UK, to produce lay summaries of all open trial protocols so as to make them freely available to patients and families through the CancerHelp UK website. A number of these have now been completed and more will come on line in the coming months. These can be found at http://www.cancerhelp.org.uk/trials/trials/default.asp. Click on 'Children's' in the drop down menu that appears for a list of all trial summaries, including those for neuroblastoma.
A phase III trial of an antibody agent opened in the UK in December 2009 as an additional element in the complex treatment protocol for children with high risk disease. Download the Cancer Research UK press release here for further details.
International Co-operation
UK researchers and clinicians have been very successful in running clinical trials, initially at a national level in the 1970s, then on a small European level in the 1980s. Since 2000 the UK has been part of a broad international group (SIOPEN) encompassing up to 36 different countries in some trials. SIOPEN is dedicated to improving the cure rate for children with neuroblastoma. There are regular world-wide meetings of international experts to discuss latest research and treatment, as well as frequent meetings of SIOPEN members to refine the way that the disease will be tackled.
SIOPEN works in partnership with the Children's Oncology Group (COG) in America so that trials can be run in parallel in order to speed up the discovery of successful treatments. We, the Neuroblastoma Society Trustees, are working with other parent groups across Europe in order to see how we can support the important work being undertaken by SIOPEN through financial support and business expertise.
Throught involvement with SIOPEN and by personal contact with a network of colleagues in other countries parents can be confident the UK clinicians and researchers are well aware of international developments in neuroblastoma research and treatment. All neuroblastoma treatment given in the UK will reflect the best established protocols for dealing with the various stages of disease and parents can have confidence that their child is getting the best care and attention possible.
International Travel Bursary
Advances in Neuroblastoma Research is a biannual international conference providing a forum for leading neuroblastoma experts across the world to meet and discuss latest developments in basic research and clinical applications of their work. The 2008 conference was held in Japan during May. The Society awarded a travel bursary for a UK researcher to attend in order to present his work and to provide a report on the conference. Download Duncan Ayers' report.