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.”

Notes

1. External Research Funding:

Leukaemia & Lymphoma Research (M Greaves and T Enver)

The Kay Kendall Leukaemia Fund (M Greaves)

2. The report was published in the journal Nature on 20 January under the title ‘Genetic variegation of clonal architecture and propagating cells in leukaemia’. 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

3. 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 here.

Source:
Institute of Cancer Research (ICR)
Oxford University’s Medical Sciences Division
UCL