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Scientists have pinpointed an enzyme responsible for breaking down and inactivating
a key childhood leukaemia drug, which could help to explain why around 20% of
patients do not respond to therapy. Their findings are published in the Journal
of Clinical Investigation today (Monday).
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% 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% 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.
Around 20% of ALL patients are thought to have cancer cells that produce AEP,
and so will not respond to Asnase.
Dr David Grant, Scientific Director of Leukaemia Research, said:
"Asparaginase has been in use for over 40 years and it continues
to be an essential element of treatment of ALL in adults and children. Almost
as soon as it entered use, asparaginase resistance was recognized as a problem;
this tremendously exciting work offers both an explanation of how that resistance
may arise and a possibility of modifying the drug to overcome resistance.
Researchers and clinicians have transformed childhood ALL from a virtual
death sentence to an illness curable in over 80 per cent of cases. This still
means that about one in five will not survive and many children who do survive
have long-term side effects. This research is still at the laboratory stage
and there is a long process ahead to translate this into clinical benefit
but it offers hope of overcoming one of the obstacles to curing all children
with ALL."
Professor Sir David Lane, chief scientist at Cancer Research UK, said:
"These encouraging results are a significant step forward in developing
'personalised treatment' – where therapy is tailored to the requirements
of an individual patient.
This concept is now becoming a reality and we look forward to seeing
if this discovery can be translated to benefit children with cancer. Our goal
is to control or cure cancer in all children."
Cancer Research UK
Together with its partners and supporters, Cancer Research UK's vision is
to beat cancer.
*
Cancer Research UK carries out world-class research to improve
understanding of the disease and find out how to prevent, diagnose and treat
different kinds
of cancer.
* Cancer Research UK ensures that its findings are used to improve the lives
of all cancer patients.
* Cancer Research UK helps people to understand cancer, the progress that is
being made and the choices each person can make.
* Cancer Research UK works in partnership with others to achieve the greatest
impact in the global fight against cancer.
For further information about Cancer Research UK's work or to find out how
to support the charity, please call 020 7009 8820 or visit their website (link
at bottom of this page).
News is included on the IvyRose website to inform visitors about current health
issues, but not to endorse any particular view or activity. Any views expressed
in the article above are not necessarily those of IvyRose Ltd.. Material in
this news item was released by Cancer Research UK on 8
June 2009 and may have been edited (e.g. in style,
length, and/or for ease of understanding by our international readers) for inclusion
here. For further information, please visit their website.
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