Wednesday 15 December 2010
A breakthrough study has shed light on the reason why advanced cancers are notoriously resistant to treatment and, remarkably, it may be as fundamental as evolution itself.
Scientists at The Institute of Cancer Research in Sutton and the University of Oxford discovered that cancer stem cells in the most common childhood leukaemia have complex and diverse combinations of mutations, even within individual patients.
Cancer stem cells have been widely regarded as the ‘bull’s eye’ for drugs to target. However, these findings suggest that there is no single bull’s eye but rather multiple targets that are constantly shifting.
Principal author of the report, Professor Mel Greaves of The Institute of Cancer Research, said: “Our research may help explain why advanced cancers remain so difficult to eradicate. A massive investment is being made in developing new drugs for advanced cancer that target the tumours’ specific genetic mutations as potential ‘Achilles heels’. Whilst some of the new drugs show considerable promise, it is important to recognise that these genetic mutations are constantly evolving, which has the potential to create lethal resistance.”
This new study, funded by the blood cancer charity Leukaemia & Lymphoma Research and published in the journal Nature, has revealed that cancer clones evolve in a Darwinian fashion by ongoing genetic variation and natural selection in the body.
The scientists showed that in the very early stages of the disease the original cancer stem cell produces distinct ‘sub-clones’ of itself. Each of these sub-clones contains different combinations of genetic mutations and will go on to develop further sub-clones independently of each other, like branches. While some sub-clones will be destroyed by drugs, other branches may be resistant to treatment and become dominant, driving the cancer forward.
Co-author of the report, Professor Tariq Enver, now of the UCL Cancer Institute, who led the research at the Weatherall Institute of Molecular Medicine, University of Oxford, said: “Our research suggests that drugs are more likely to be effective for longer if they target properties shared by all cancer stem cells in each patient, so this is an important area for further investigation. It also endorses the view that early intervention or, where possible, prevention, is likely to be more effective.”
Dr David Grant, Scientific Director at Leukaemia & Lymphoma Research, said: “These findings are very exciting and represent a big step forward in our understanding of how childhood leukaemia develops. It has huge practical implications and it will be important to assess, as is likely, if this model of cancer stem cell development holds true for other types of leukaemia and cancer in general.”
Media contact: Henry Winter at the Leukaemia & Lymphoma Research Press Office on 020 7269 9019, 07824 375880 or email: [email protected]
Notes to editors:
Genetic variegation of clonal architecture and propagating cells in leukaemia publishes online on December 15 in the journal Nature. Principal authors: Professor Mel Greaves of The Institute of Cancer Research, Sutton, and Professor Tariq Enver of MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford
External Research Funding:
Leukaemia & Lymphoma Research (M Greaves and T Enver)
The Kay Kendall Leukaemia Fund (M Greaves)
Leukaemia & Lymphoma Research is the only UK charity solely dedicated to research into blood cancers, including leukaemia, lymphoma and myeloma. These cancers are diagnosed in around 28,500 children, teenagers and adults in the UK every year. Leukaemia & Lymphoma Research was previously known as Leukaemia Research and has changed its name to raise awareness of its longstanding commitment to research into all the blood cancers - not just leukaemia.
We celebrate our 50th anniversary in 2010 and our expertise and focus enables us to invest in only the best UK research into better diagnosis, treatments and cures. As we receive no government funding and rely entirely on voluntary support, we need to raise £120 million in the next five years to continue this life-saving research. Further information, including patient information booklets, is available from www.beatbloodcancers.org or on 020 7405 0101.
The Institute of Cancer Research (ICR)
- The ICR is Europe’s leading cancer research centre
- The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise
- The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe
- The ICR has charitable status and relies on voluntary income, spending 90 pence in every pound of total income directly on research
- As a college of the University of London, the ICR also provides postgraduate higher education of international distinction
- Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world
For more information visit www.icr.ac.uk
Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University’s income and expenditure, and two-thirds of its external research income. Oxford’s world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.
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