Abstract
Cancer cells rapidly evolve drug resistance through somatic evolution and, in order to continue growth in the metastatic phase, violate the organism-wide consensus of regulated growth and beneficial communal interactions. We suggest that there is a fundamental mechanistic connection between the rapid evolution of resistance to chemotherapy in cellular communities within malignant tissues and the rapid evolution of antibiotic resistance in bacterial communities. We propose that this evolution is the result of a programmed and collective stress response performed by interacting cells, and that, given this fundamental connection, studying bacterial communities can provide deeper insights into the dynamics of adaptation and the evolution of cells within tumours.
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Acknowledgements
We wish to thank D. Coffey and A. Barker for their helpful comments. The research described was supported by award U54CA143803 from the US National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Cancer Institute or the US National Institutes of Health.
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FURTHER INFORMATION
Glossary
- Altruism
-
Behaviours that benefit another individual while incurring a cost to oneself.
- Biofilm
-
A multicellular aggregate of bacteria and its associated proteinaceous matrix formed in response to external stress.
- Cheating
-
A strategy in which individuals do not cooperate but still benefit from the positive interactions with cooperating individuals.
- Clonal expansion
-
Population growth that is mainly carried out by a single genotype.
- Cooperation
-
Actions or behaviours that are beneficial to other individuals.
- Cystic fibrosis
-
An inherited disease that causes thick mucus to build up in the lungs and the digestive tract.
- Cytocidal agent
-
A molecule or drug causing cell death.
- Exopolymer matrix
-
A polysaccharide-based extracellular matrix collectively secreted by bacteria in biofilms. The matrix links cells together and acts as a protective microenvironment.
- Game theory
-
A mathematical theory describing the costs and benefits associated with the interactions among individuals of a group. This theory is most often used in economics and evolutionary biology.
- Genetic drift
-
A process through which the frequency of genes in populations fluctuates because selection occurs mainly by chance.
- Growth advantage under stationary phase
-
(GASP). A phenotype that allows certain bacterial cells to outcompete wild-type cells by maintaining a proliferative state while the wild-type cells cease to grow and enter stationary phase.
- Phenotypic switching
-
The ability of organisms to alternate between two distinct states in order to adapt to fluctuating environments.
- Retromutagenesis
-
A process whereby DNA damage that causes changes to base pairing becomes incorporated into the genome. This may occur if a mutant protein resulting from transcriptional mutagenesis causes the rapid restart of DNA replication, thus resulting in a genetic lesion that alters base pairing being copied by a DNA polymerase before the lesion is repaired and thereby altering the DNA sequence.
- SOS response
-
A global DNA damage response in bacteria that involves cell cycle arrest and mutagenic DNA repair and recombination.
- Source–sink ecology
-
A theoretical model used to describe the dynamics of a population inside habitats that either promote growth (source) or induce death (sink).
- Transcriptional mutagenesis
-
A process by which proteins with altered functions are translated because RNA polymerases transcribe mRNA from a template containing DNA damage.
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Lambert, G., Estévez-Salmeron, L., Oh, S. et al. An analogy between the evolution of drug resistance in bacterial communities and malignant tissues. Nat Rev Cancer 11, 375–382 (2011). https://doi.org/10.1038/nrc3039
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DOI: https://doi.org/10.1038/nrc3039
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