A breakthrough study on childhood leukaemia stem cells has shed light on 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.
Professor Mel Greaves of The Institute of Cancer Research, who led the study, said: “Our research may help explain why advanced cancers remain so difficult to cure. A massive investment is being made developing new drugs for advanced cancers that target specific genetic mutations thought to be the ‘Achilles heels’. Whilst some of the new drugs show promise, it is important to recognise that these genetic mutations are constantly evolving, creating new targets. This has the potential to create resistance and can make blood cancers difficult to treat.”
This new Leukaemia & Lymphoma Research study, which was published in the journal Nature in December, has revealed that cancer clones evolve in a Darwinian fashion by continuous 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, others may be resistant to treatment and become dominant, driving the cancer forward.
Co-researcher, Professor Tariq Enver, then 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 a more effective route to finding a cure.”
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 also has huge implications for the development of new and more effective treatments. Further research will shed light on whether these findings can be applied to cancer stem cell found in other types of blood cancer.”