Scientists have uncovered the genetic causes of a rare but lethal form of childhood cancer – opening up the prospect of an effective treatment for the disease for the first time.
The team at The Institute of Cancer Research, London, has discovered a mechanism driving the development of childhood glioblastoma, a form of brain cancer in children for which no drug treatments are available.
Drugs targeted at the genetic mechanism have already been developed for use in other cancer types, and the researchers plan to test these in clinical trials of children within two to three years.
The results, published online in the journal Cancer Discovery today (Thursday), could offer some hope for children with glioblastoma, who currently only survive for a year on average from diagnosis. The study received funding from a number of organisations including Cancer Research UK, the Wellcome Trust, The Brain Tumour Charity, The Stavros Niarchos Foundation and Breakthrough Breast Cancer.
The researchers showed that mutation of a histone protein called H3F3A – which acts as a gene scaffold – unleashes a chain of genetic activity that can lead to the development of glioblastomas. Specifically, this mechanism switches on a gene called MYCN which is known to cause cancer.
There are drugs currently in clinical trials for other types of cancer which can block MYCN’s activity, and it is possible these could become effective treatments for glioblastoma, and help extend the lives of the young patients affected.
Study author Dr Chris Jones, leader of the glioma team at The Institute of Cancer Research (ICR), said: “Our research greatly improves our understanding of the genetic origins of childhood glioblastoma, and identifies key targets for drug treatment of the disease. At present, childhood glioblastoma is an almost certain death sentence for those who develop it, but we now have some hope that effective treatments may be on the horizon. We want to start testing out our ideas in clinical trials as soon as we can – within the next two to three years.”
The researchers started out by confirming previous work suggesting that childhood glioblastoma was more than one disease, and that the different types develop in different areas and at different ages. One type affects younger children aged from about six years; the other, children and young adults aged 13 and over. About 60 children develop childhood glioblastoma in the UK each year.
The ICR team showed that the pattern of gene activity was sufficiently different in the types affecting older and younger children to justify the claim that they were different diseases. Following this, they looked at cells from a patient with the form of the disease affecting older children, characterised by mutations in a particular position in the histone protein, and discovered that the MYCN gene was highly active.
The team then ran a large-scale screening experiment to see which drugs might be effective in blocking the cancer-causing effect of the MYCN gene. They identified a drug target called aurora kinase A, for which drugs are already being developed. These drugs can now be tested in the particular group of childhood glioblastoma patients with the histone mutation.
Professor Paul Workman, Deputy Chief Executive of The Institute of Cancer Research and study co-author, said: “Advances in technology are rapidly transforming our understanding of the genetic causes of cancer. Studies like this one pinpoint the precise set of genes that appear to be driving a cancer’s development, and give us targets for the next generation of cancer drugs. And in this case, there are realistic hopes that drugs already under development for other cancers could be used for childhood glioblastoma too.”
ENDS
For more information and interviews contact Claire Bithell in The Institute of Cancer Research media team on 020 7153 5312 / [email protected]. For out of hours enquiries please contact 07969 082520
Notes to editor
The Institute of Cancer Research, London, is one of the world’s most influential cancer research institutes.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR’s mission is to make the discoveries that defeat cancer. For more information visit www.icr.ac.uk
About Cancer Research UK
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