Monday 28 September 2009
Scientists have found strong evidence that two genetic abnormalities are linked to children developing the most common type of brain tumour, according to research published this month in the journal Clinical Cancer Research.
The research led by the Institute of Cancer Research (ICR) raises the possibility that existing cancer drugs may be able to treat children with high-grade gliomas.
Scientists had previously found that a genetic abnormality – carrying too many copies of a gene called epidermal growth factor receptor (EGFR) – occurred in about 40 per cent of adult glioblastoma patients. Approximately half of these patients also had a second type of mutation in the EGFR gene. These mutations were not considered important in childhood brain cancer but, until now, a conclusive study had not been done.
In the largest ever study of EGFR gene alterations in such patients, scientists from the UK, France, Portugal, Brazil and the US examined 90 samples from children who had high-grade – fast growing and often fatal – gliomas.
“We found the EGFR gene was amplified in 10 per cent of high-grade childhood glioma cases. Many of these tumours also had the deletion mutation – the first time this has ever been found in children,” says study leader Dr Chris Jones, who heads the ICR’s Paediatric Molecular Pathology Team.
Drugs that target the EGFR gene have been used in clinical trials to treat adult glioblastomas, so the scientists next investigated whether these drugs could also help children.
In laboratory tests, they treated childhood glioma cells carrying the EGFR deletion mutation with a drug called erlotinib (Tarceva), which blocks the EGFR gene. But the drug did not kill the cancer cells, and in further tests the scientists identified a molecule specific to the children’s cells – platelet-derived growth factor receptor – that prevented the drug from being effective.
So the team next used erlotinib in combination with another drug called imatinib (Glivec), which aimed to block the other molecule. They found significant death of cancer cells when the two drugs were used together.
“Our study provided strong laboratory evidence that these two drugs could be used in combination to treat some childhood gliomas,” Dr Jones says. “A future step would be to undertake further lab research and then test these drugs in patients.”
Members of the research team received funding support from Cancer Research UK, Breakthrough Breast Cancer, the Department of Health, the Oak Foundation and La Fondation de France.
Media Contact: ICR Science Press Officer Jane Bunce on [email protected] or 0207 153 5106 or after hours 07721747900
Note to editors:
• Gliomas are tumours that develop from glia, a type of brain cell
• Gliomas account for about 80 per cent of primary malignant brain tumours (cancer that originates in the brain)
• Glioblastomas are a type of high grade (aggressive) glioma that are often fatal
• In the UK, about 4,550 adults and 350 children are diagnosed with brain tumours each year
• Brain tumours can be very difficult to treat successfully and sadly only 14 per cent of people diagnosed with a brain tumour are alive after five years
• Erlotinib is a drug that targets EGFR and is already licensed to treat several types of cancer, in particular pancreatic and lung
• Imatinib, a well-known drug with the brand name Gleevec (US) or Glivec (Europe/Australia), is already used to treat chronic myelogenous leukemia, gastrointestinal stromal tumours and a number of other cancers. Its normal action is to block tyrosine kinase enzymes, but is also being tested in the lab to supress platelet-derived growth factor
The Institute of Cancer Research
The Institute of Cancer Research (ICR) is Europe’s leading cancer research centre with expert scientists working on cutting-edge research. In 2009, the ICR marks its 100 years of groundbreaking research into cancer prevention, diagnosis and treatment. In December 2008, the ICR was ranked as the UK’s leading academic research centre by the Times Higher Education’s Table of Excellence, based on the results of the Higher Education Funding Council’s Research Assessment Exercise. It’s home to the world’s leading academic paediatric childhood cancer drug development unit. In the next 10 years our scientists aim to develop effective drugs to treat the four cancers responsible for the majority of childhood cancer deaths. To achieve this and our other research, the ICR – as a charity - relies on voluntary income, for more information visit www.icr.ac.uk