Scientists have pinpointed an enzyme responsible for breaking down and inactivating a key childhood leukaemia drug, which could help to explain why around 20 per cent of patients do not respond to therapy. Their findings are published in the Journal of Clinical Investigation.
The researchers, funded by Cancer Research UK and Leukaemia Research, also discovered that the enzyme - called AEP - was not found in healthy white blood cells, which are the cells affected by leukaemia.
So production of AEP and resistance to the drug is the result of a genetic fault in some leukaemia cells**.
Over 80 per cent of children with acute lymphoblastic leukaemia (ALL) are successfully treated, but for some patients the treatment does not work. So it is crucial that new treatments are found to help ensure all children with this type of cancer are cured.
Asnase is a form of a drug called Asparaginase and is used to treat all children with ALL in the UK. It is produced commercially using the bacteria E. coli.
Around 20 per cent of ALL patients become resistant to the drug or have an allergic reaction.
The scientists found that AEP breaks down Asnase and so stops the drug from working. They think that the presence of AEP could determine whether patients respond to Asnase treatment, and whether they have an allergic reaction to it.
If these results are confirmed in patients, a test could one day be developed to help doctors predict whether children with ALL will benefit from Asnase before treatment starts and hopefully prevent some patients undergoing unnecessary chemotherapy.
Professor Vaskar Saha, Cancer Research UK's paediatric oncologist, based at the Paterson Institute in Manchester, said: "Although our results are at an early stage, our study is an important development in understanding the science behind why some patients don't respond to leukaemia drugs.
"If our findings in leukaemia cells are confirmed in patients, we could be able to test if this drug is the best option before treatment starts - we're currently recruiting patients from 18 childhood cancer centres in the UK to help us discover if this is the case."
Dr Paul Bates, study co-author based at Cancer Research UK's London Research Institute, said: "We are now looking at how to modify the drug to make it more potent and resistant to AEP's actions."
ALL is the most common type of childhood cancer, and accounts for one in four of all cancers in children in the UK - around 450 cases are diagnosed each year.