Abstract
Acquired drug resistance in cancer results from Darwinian selection and evolution among cancer cells, fuelled by their cell-heritable heterogeneity. As a consequence, targeted therapies are generally not curative or sustainably effective. Avoiding acquired resistance during therapy will require alternatives to the standard drug classes, such as cytotoxins, that are known to drive cancer’s evolutionary response towards acquired resistance. Important characteristics of cancer cannot be attributed solely to the individual cells composing it, but instead emerge as collective properties of the population of cancer cells. Such collective properties do not vary among individual cells and thus do not provide fuel for cellular selection and the resulting evolution of acquired drug resistance Therapies that target collective cooperation among pathogen cells instead of targeting the cells themselves have been called ‘antisocial’ therapies. Theory predicts that antisocial therapies will delay acquired drug resistance and retain effectiveness better than cytotoxins can. Empirical results have supported this prediction for other cellular pathogens, but it has yet to be tested carefully in cancer. Doing so should be a high priority.
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Glossary
- Acquired drug resistance
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A situation where a cancer that is initially susceptible to a therapeutic drug becomes resistant to it during therapy often leading to tumour re-growth and patient relapse
- Tumour heterogeneity
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The observation that cells within the same tumour differs in their genes and their traits
- Antisocial therapies
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A class of therapeutic drugs that block the ability of cancer cells to provide mutual benefits to each other rather than killing susceptible cancer cells directly (and selectively)
- Darwinian evolution
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Population change by natural selection in which only those individuals (or cells) best able to survive and reproduce in a given environment will pass on their genes to the next generation, with the result that only those genes and traits allowing the most survival and reproduction will persist over time
- Somatic cells
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In contrast to germ cells (eggs and sperm) that create offspring somatic (within-body) cells make up the tissues of an individual during its single lifetime. Mutations in these cells can change cell traits and be inherited by daughter somatic cells, but are not passed on to offspring
- Cytotoxin
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A drug to kill cells often of a single targeted type (‘targeted cytotoxins’)
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Pepper, J.W. (2016). Darwinian Strategies to Avoid the Evolution of Drug Resistance During Cancer Treatment. In: Alvergne, A., Jenkinson, C., Faurie, C. (eds) Evolutionary Thinking in Medicine. Advances in the Evolutionary Analysis of Human Behaviour. Springer, Cham. https://doi.org/10.1007/978-3-319-29716-3_12
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DOI: https://doi.org/10.1007/978-3-319-29716-3_12
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