Darwin’s theory of evolution by natural selection – a force of nature favouring those carrying advantageous traits and making those traits more common in the next generation – is the central paradigm of biology. Darwin developed this idea to explain the origins of the extraordinary diversity of species on the planet. But it turns out that exactly the same fundamental principle applies to many areas of health and disease, including antibiotic resistance, the emergence of new infectious diseases, the functioning of our immune systems and, not least, cancer.
Evolution already has some important applications in the world of medicine, neatly illustrated by the example of antibiotic resistance in bacteria. When a drug is used on a species of bacteria, those that are sensitive will die and do not go on to reproduce. But bacteria that carry a resistance gene, either as a pre-existing trait or through a new mutation, survive to pass on drug resistance to the next generation. And just as the dynamics of evolution are at play within a petri dish of antibiotic-treated bacteria, so they are within the complex environment of a tumour.
One of the pioneers of applying evolutionary thinking to cancer research is Professor Mel Greaves, an expert in the biology of leukaemias here at The Institute of Cancer Research, London. Professor Greaves says: “The three big cancer medicine questions we are asking, are based on the principles of evolutionary biology: why are humans so vulnerable to cancer; what determines the protracted and unpredictable development of cancers in the body over years or decades; and why are we seeing drug resistance so frequently?”
In a quest to seek these answers, the ICR has established the Centre for Evolution and Cancer. The centre is the first of its kind and scale in the world, and has been possible thanks to start-up funding from some of our philanthropic donors and from members of The Discovery Club. Leading the centre, Professor Greaves says: “Across the world, there are many small-sized teams of specialists investigating various areas of cancer causation, cancer biology and drug resistance mechanisms from an evolutionary biology standpoint. While our researchers are currently involved in and actively support the collaborative interactions of these worldwide efforts, we believe the time is right for a more focused and concerted effort in this area. We are ideally placed in this respect as Europe’s largest comprehensive cancer centre where both the basic evolutionary biology of cancer and its translational clinical application can be vigorously pursued.”
Computational biologists, geneticists, cell biologists and clinical scientists – including individuals trained in evolutionary ecology – will all come together to explore exciting new avenues of cancer-related evolutionary research. Researchers will identify the genetic diversity within each sub-clone in individual tumours, and explore their use as fingerprints that could predict progression of disease, metastases or drug resistance. Professor Greaves explains: “By monitoring and measuring clonal evolution – cell proliferation and the acquisition of mutations – we may be able to develop new tools to predict cancer outcomes. This will also give us a map of the clonal, genetic architecture of each cancer clone, and we may be able to reveal both its phylogenetic history and pinpoint the ‘founder’ mutation, using this as a target for therapy. As Darwinian selection for drug resistance operates at the level of single cancer ‘stem’ cells, we will be tracking the frequency and genetic diversity of these key cells, and their ecosystem dependence. This should open up the opportunities for both prognostic tests and therapeutic intervention.”
Going beyond the tumour itself, researchers will look at the microenvironment that provides positive selective pressures for cancer cell evolution. As cancer clones all evolve dynamically within the habitats of our tissues on which they retain some dependence, therapeutic regulation of the ecosystem may be a viable alternative to the current notion of trying to directly kill cancer cells – a bit like draining the swamps to get rid of mosquitoes, as one way of eradicating malaria. In fact, anti-hormonal therapies, anti-inflammatories – such as aspirin – and anti-angiogenesis therapies already do this.
Some of the ambitious questions researchers will want to address surround understanding the origins of cancer. Evidence now suggests that breast and prostate cancer may be so common because of a mismatch that has occurred between ancestral and current lifestyles with respect to reproduction. Professor Greaves says: “Maybe we should be viewing these cancers as trade-offs of increased fertility, and the inherited genes that are conferring susceptibility to these cancers as the legacy of prior selection for this increased fertility. And if this is the case, we can set about modelling it, and could possibly prevent the evolution of these cancers by hormonal manipulation.”
Evolution by natural selection is taking place in every conceivable place within the Earth’s biosphere. It’s the ultimate race of life where the fittest will win, driving extraordinary feats of survival. Opportunities for applying a Darwinian perspective to cancer are also remarkable. With this comes the prospect of a radically different way of thinking about cancer, its causes and treatment. It is potentially a paradigm shift and opens up new opportunities for exploring the fundamentals of cancer, and new avenues for treatment and prevention.
Darwin’s theory of evolution by natural selection – a force of nature favouring those carrying advantageous traits and making those traits more common in the next generation – is the central paradigm of biology. Darwin developed this idea to explain the origins of the extraordinary diversity of species on the planet. But it turns out that exactly the same fundamental principle applies to many areas of health and disease, including antibiotic resistance, the emergence of new infectious diseases, the functioning of our immune systems and, not least, cancer.
Evolution already has some important applications in the world of medicine, neatly illustrated by the example of antibiotic resistance in bacteria. When a drug is used on a species of bacteria, those that are sensitive will die and do not go on to reproduce. But bacteria that carry a resistance gene, either as a pre-existing trait or through a new mutation, survive to pass on drug resistance to the next generation. And just as the dynamics of evolution are at play within a petri dish of antibiotic-treated bacteria, so they are within the complex environment of a tumour.
One of the pioneers of applying evolutionary thinking to cancer research isProfessor Mel Greaves, an expert in the biology of leukaemias here at The Institute of Cancer Research, London. Professor Greaves says: “The three big cancer medicine questions we are asking, are based on the principles of evolutionary biology: why are humans so vulnerable to cancer; what determines the protracted and unpredictable development of cancers in the body over years or decades; and why are we seeing drug resistance so frequently?”
In a quest to seek these answers, The Institute of Cancer Research (ICR) has established the Centre for Evolution and Cancer. The centre is the first of its kind and scale in the world, and has been possible thanks to start-up funding from some of our philanthropic donors and from members of The Discovery Club. Leading the centre, Professor Greaves says: “Across the world, there are many small-sized teams of specialists investigating various areas of cancer causation, cancer biology and drug resistance mechanisms from an evolutionary biology standpoint. While our researchers are currently involved in and actively support the collaborative interactions of these worldwide efforts, we believe the time is right for a more focused and concerted effort in this area. We are ideally placed in this respect as Europe’s largest comprehensive cancer centre where both the basic evolutionary biology of cancer and its translational clinical application can be vigorously pursued.”
Computational biologists, geneticists, cell biologists and clinical scientists – including individuals trained in evolutionary ecology – will all come together to explore exciting new avenues of cancer-related evolutionary research. Researchers will identify the genetic diversity within each sub-clone in individual tumours, and explore their use as fingerprints that could predict progression of disease, metastases or drug resistance. Professor Greaves explains: “By monitoring and measuring clonal evolution – cell proliferation and the acquisition of mutations – we may be able to develop new tools to predict cancer outcomes. This will also give us a map of the clonal, genetic architecture of each cancer clone, and we may be able to reveal both its phylogenetic history and pinpoint the ‘founder’ mutation, using this as a target for therapy. As Darwinian selection for drug resistance operates at the level of single cancer ‘stem’ cells, we will be tracking the frequency and genetic diversity of these key cells, and their ecosystem dependence. This should open up the opportunities for both prognostic tests and therapeutic intervention.”
Going beyond the tumour itself, researchers will look at the microenvironment that provides positive selective pressures for cancer cell evolution. As cancer clones all evolve dynamically within the habitats of our tissues on which they retain some dependence, therapeutic regulation of the ecosystem may be a viable alternative to the current notion of trying to directly kill cancer cells – a bit like draining the swamps to get rid of mosquitoes, as one way of eradicating malaria. In fact, anti-hormonal therapies, anti-inflammatories – such as aspirin – and anti-angiogenesis therapies already do this.
Some of the ambitious questions researchers will want to address surround understanding the origins of cancer. Evidence now suggests that breast and prostate cancer may be so common because of a mismatch that has occurred between ancestral and current lifestyles with respect to reproduction. Professor Greaves says: “Maybe we should be viewing these cancers as trade-offs of increased fertility, and the inherited genes that are conferring susceptibility to these cancers as the legacy of prior selection for this increased fertility. And if this is the case, we can set about modelling it, and could possibly prevent the evolution of these cancers by hormonal manipulation.”
Evolution by natural selection is taking place in every conceivable place within the Earth’s biosphere. It’s the ultimate race of life where the fittest will win, driving extraordinary feats of survival. Opportunities for applying a Darwinian perspective to cancer are also remarkable. With this comes the prospect of a radically different way of thinking about cancer, its causes and treatment. It is potentially a paradigm shift and opens up new opportunities for exploring the fundamentals of cancer, and new avenues for treatment and prevention.
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