Evolutionary Processes in Cancer
- LAST MODIFIED: 12 January 2022
- DOI: 10.1093/obo/9780199941728-0139
- LAST MODIFIED: 12 January 2022
- DOI: 10.1093/obo/9780199941728-0139
Cancer develops through the evolution of somatic cells in multicellular bodies. The familiar dynamics of organismal evolution, including mutations, natural selection, genetic drift, and migration, also occur among the cells of multicellular organisms. In some cases, but not all, these evolutionary processes lead to cancer. This has profound implications for both our understanding of cancer and our treatment of the disease, as well as its prevention. All of our medical interventions impose selective pressures on the heterogeneous populations of billions of cells in tumors, and tend to select for mutant cells that are resistant to the intervention, regardless of whether the intervention is a drug, radiation, the immune system, or anything else that has been tried. We will likely need evolutionary and ecological approaches to cancer to manage its evolution in response to our interventions. The field of the evolutionary biology and ecology of cancer is still young and relatively small. We are in the early stages of translating ideas and tools from evolutionary biology and ecology to study and manage cancers. There is a desperate need for more researchers with expertise in evolutionary biology and ecology to apply their skills and ideas to cancer. Currently, there are far more important questions that need to be addressed than there are people to address them.
The idea that cancers are generated by cell-level evolutionary processes was introduced in Nowell 1976 and Cairns 1975. Over the last forty-plus years, the evolutionary theory of cancer has stood the test of time, including hundreds, if not thousands, of experimental and clinical tests of the concepts. These include documentation of the evolution of acquired resistance to therapies, genetic and epigenetic heterogeneity within neoplasms, heritability of that variation, and expansion of clones with adaptive mutations. As such, the evolutionary model of cancer can be reasonably elevated to the status of a scientific theory. However, after Nowell 1976, the evolutionary biology of cancer was largely ignored by the cancer research community throughout the rest of the 20th century, perhaps in part due to the dominance of simple, linear models of carcinogenesis pioneered by Vogelstein and colleagues (see Vogelstein, et al. 1988). The evolutionary biology of cancer has only really gained attention in the 21st century, starting with Merlo, et al. 2006, which reviewed how the different components of evolutionary and ecological theory apply to cancer. Greaves and Maley 2012 updates this review, and Aktipis and Nesse 2013 provides a more accessible overview appropriate for an undergraduate student audience that also includes a discussion of the evolution of susceptibility and resistance to cancer at the organismal level. More recent reviews have emphasized clinical relevance, with McGranahan and Swanton 2015 focusing on the importance of intratumor heterogeneity for the clinic, and a community wide effort in Maley, et al. 2017 to develop classification systems of the types of evolution and ecologies in tumors to help clinicians develop better management strategies for cancers.
Aktipis, C., and R. M. Nesse. 2013. Evolutionary foundations for cancer biology. Evolutionary Applications 6.1: 144–159.
This is probably the most accessible overview of the evolutionary theory and ecology of cancer. It uses an evolutionary medicine framing of the different reasons for human susceptibility to cancer, and also discusses the role of cancer as a selective force in organismal evolution more generally in the context of the evolution of multicellularity. This paper is often used in undergraduate classes to cover these topics.
Cairns, J. 1975. Mutation selection and the natural history of cancer. Nature 255:197–200.
A year prior to Nowell’s foundational paper, John Cairns argued that the subdivision of tissues into proliferative units, like the crypts of the intestine, effectively prevented mutant stem cells from expanding beyond the small number of stem cells within a crypt, and that the tissue architecture thus acts as a tumor suppressor. He also predicted that stem cells would preserve the same unsynthesized “immortal” strand of their DNA every time they divide as a mechanism to reduce mutations in stem cells.
Greaves, M., and C. C. Maley. 2012. Clonal evolution in cancer. Nature 481.7381: 306–313.
An update of Merlo, et al. 2006 reviewing the evolutionary theory of cancer including a discussion of driver mutations in cancer, the tempo and mode of cell level evolution in neoplasms, and evolutionary approaches to therapy.
Maley, C. C., A. Aktipis, T. A. Graham, et al. 2017. Classifying the evolutionary and ecological features of neoplasms. Nature Reviews. Cancer 17.10: 605–619.
This is a consensus statement from the community of researchers in the field of the evolution and ecology of cancer that lays out a framework for developing classification systems of the type of evolution and ecology occurring in a given tumor. It includes an updated overview of the evolution and ecology of cancer.
Merlo, L. M., J. W. Pepper, B. J. Reid, and C. C. Maley. 2006. Cancer as an evolutionary and ecological process. Nature Reviews. Cancer 6.12: 924–935.
An overview of the basic components of evolutionary theory and ecology as applied to the somatic evolution of neoplasms.
McGranahan, N., and C. Swanton. 2015. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell 27.1: 15–26.
This review emphasizes the clinical implications of cancer evolution including precision medicine efforts, drivers of progression, therapeutic resistance, and immunotherapy.
Nowell, P. C. 1976. The clonal evolution of tumor cell populations. Science 194.4260: 23–28.
The foundational paper that laid out the evolutionary theory of cancer. Cytogenetic evidence from hematopoietic cancers made it clear that somatic cells develop chromosomal aberrations associated with large expansions of the clones carrying those aberrations. Following patients over time showed clones acquire further chromosomal abnormalities, in clear examples of “descent with modification” at the cellular level. Nowell predicted that this process could explain metastases as well as therapeutic resistance.
Vogelstein, B., E. R. Fearon, S. R. Hamilton, et al. 1988. Genetic alterations during colorectal-tumor development. New England Journal of Medicine 319.9: 525–532.
This paper established a paradigm of a linear sequence of mutational events leading to cancer (based on a flawed methodology). We now know that neoplasms do not have a linear sequence of mutations, but rather that each neoplasm represents a cell lineage tree with many different sequences. We also know that there are often many different sets of mutations and sequences that can produce any given type of cancer.
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- Adaptive Radiation
- Ancient DNA
- Behavioral Ecology
- Canalization and Robustness
- Cancer, Evolutionary Processes in
- Character Displacement
- Cognition, Evolution of
- Constraints, Evolutionary
- Contemporary Evolution
- Convergent Evolution
- Cooperation and Conflict: Microbes to Humans
- Cooperative Breeding in Insects and Vertebrates
- Cryptic Female Choice
- Darwin, Charles
- Disease Virulence, Evolution of
- Diversification, Diversity-Dependent
- Ecological Speciation
- Epigenetics and Behavior
- Epistasis and Evolution
- Eusocial Insects as a Model for Understanding Altruism, Co...
- Evidence of Evolution, The
- Evolution and Development: Genes and Mutations Underlying ...
- Evolution and Development of Individual Behavioral Variati...
- Evolution, Cultural
- Evolution of Animal Mating Systems
- Evolution of Antibiotic Resistance
- Evolution of New Genes
- Evolution of Plant Mating Systems
- Evolution of Specialization
- Evolutionary Biology of Aging
- Evolutionary Biomechanics
- Evolutionary Computation
- Evolutionary Developmental Biology
- Evolutionary Ecology of Communities
- Experimental Evolution
- Field Studies of Natural Selection
- Founder Effect Speciation
- Frequency-Dependent Selection
- Fungi, Evolution of
- Gene Duplication
- Gene Expression, Evolution of
- Gene Flow
- Genetics, Ecological
- Genome Evolution
- Geographic Variation
- Group Selection
- History of Evolutionary Thought, 1860–1925
- History of Evolutionary Thought before Darwin
- History of Evolutionary Thought Since 1930
- Human Behavioral Ecology
- Human Evolution
- Hybrid Speciation
- Hybrid Zones
- Identifying the Genomic Basis Underlying Phenotypic Variat...
- Inbreeding and Inbreeding Depression
- Inclusive Fitness
- Innovation, Evolutionary
- Islands as Evolutionary Laboratories
- Kin Selection
- Land Plants, Evolution of
- Landscape Genetics
- Landscapes, Adaptive
- Language, Evolution of
- Latitudinal Diversity Gradient, The
- Macroevolutionary Rates
- Male-Male Competition
- Mass Extinction
- Mate Choice
- Maternal Effects
- Medicine, Evolutionary
- Meiotic Drive
- Modern Synthesis, The
- Molecular Clocks
- Molecular Phylogenetics
- Mutation Rate and Spectrum
- Mutualism, Evolution of
- Natural Selection in Human Populations
- Natural Selection in the Genome, Detecting
- Neutral Theory
- New Zealand, Evolutionary Biogeography of
- Niche Construction
- Niche Evolution
- Non-Human Animals, Cultural Evolution in
- Origin and Early Evolution of Animals
- Origin of Eukaryotes
- Origin of Life, The
- Paradox of Sex
- Parental Care, Evolution of
- Personality Differences, Evolution of
- Phenotypic Plasticity
- Phylogenetic Comparative Methods and Tests of Macroevoluti...
- Phylogenetic Trees, Interpretation of
- Polyploid Speciation
- Population Genetics
- Population Structure
- Post-Copulatory Sexual Selection
- Psychology, Evolutionary
- Punctuated Equilibria
- Quantitative Genetic Variation and Heritability
- Reaction Norms, Evolution of
- Reproductive Proteins, Evolution of
- Selection, Directional
- Selection, Disruptive
- Selection Gradients
- Selection, Natural
- Selection, Sexual
- Selfish Genes
- Sequential Speciation and Cascading Divergence
- Sexual Conflict
- Sexual Selection and Speciation
- Sexual Size Dimorphism
- Speciation Genetics and Genomics
- Speciation, Geography of
- Speciation, Sympatric
- Species Concepts
- Species Delimitation
- Sperm Competition
- Systems Biology
- Taxonomy and Classification
- Tetrapod Evolution
- The Philosophy of Evolutionary Biology
- Theory, Coalescent
- Trends, Evolutionary
- Wallace, Alfred Russel