Cancer Evolution

Abstract

Cancer is an evolutionary process of somatic cellular selection. Genetic and epigenetic alterations in tumour cell populations generate the heritable variation on which natural selection can act. The multistep process of carcinogenesis can be rationalised as the acquisition of functional traits that enable incipient cancer cells to achieve replicative success and, eventually, immortality in a tumour microenvironment. Evolution explains why cancer exists, as it is a natural consequence of selection at the cellular level, despite being harmful at the organismic level. Evolution also explains why cancer therapy fails. Therapeutic intervention may eradicate many cancer cells, but this also inadvertently clears the ecological niche and positively selects for the expansion of resistant cells. New applications of evolutionary biology, ecological theory and multilevel selection theory are deepening our understanding of cancer progression. An evolutionary perspective of cancer also offers novel prevention and treatment strategies for cancer.

Key Concepts

  • Cancer is a process of somatic selection in which variant cells acquire fitness advantages in a tumour microenvironment.
  • The hallmark capabilities of cancer cells can be understood as functional adaptations that confer a reproductive advantage over normal cells.
  • Tumours are heterogeneous populations of cells. A high amount of cancer heterogeneity is associated with an increased rate of cancer progression and a negative prognostic factor for treatment.
  • The tumour microenvironment plays a key role in cancer suppression.
  • The availability of resources in a tumour microenvironment can influence cancer development, invasion and metastasis.
  • Cancer is an example of natural selection acting in opposing directions at different levels of the biological hierarchy – an increased fitness of the cancer cell is correlated with a decreased fitness of the host organism.
  • Evolutionary medicine offers reasons for why our bodies remain vulnerable to cancer despite years of evolving powerful mechanisms for suppressing the development of cancer.
  • The application of evolutionary thinking to cancer biology is offering fresh insights on new therapeutic strategies.

Keywords: cancer; evolution; natural selection; tumour microenvironment; levels of selection

Figure 1. Cancer is a process of somatic selection. Some variant cells possess beneficial mutations that allow them to circumvent selective pressures against cancer, such as immune predation. Other cells become extinct, remain dormant or metastasise to other areas of the body.
Figure 2. (a) Heterogeneous tumour populations are expected to progress faster than homogeneous tumour populations, as there is a higher likelihood in heterogeneous populations for there to be a particular subclone that possesses a proliferative or survival advantage. (b) Heterogeneous tumour populations are also associated with negative prognostic factors, as there is a higher chance that there is a subclone already resistant to therapy in the population. Modified from Aktipis and Nesse (2013). © John Wiley & Sons Ltd published under the terms of the Creative Commons Attribution License.
Figure 3. In cancer, natural selection acts in opposing directions at different levels of the biological hierarchy. As the fitness of the cancer increases at the cellular level, the fitness of the host at the organismic level decreases. Organisms that possess good traits for cancer suppression (black) are favoured over organisms that lack these traits to keep potentially malignant cells in check (red).
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References

Aceto N, Bardia A, Miyamoto DT, et al. (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158: 1110–1122.

Aktipis CA, Maley CC and Pepper JW (2012) Dispersal evolution in neoplasms: the role of disregulated metabolism in the evolution of cell motility. Cancer Prevention Research 5: 266–275.

Aktipis CA and Nesse RM (2013) Evolutionary foundations for cancer biology. Evolutionary Applications 6: 144–159.

Aktipis CA, Boddy AM, Gatenby RA, Brown JS and Maley CC (2013) Life history trade‐offs in cancer evolution. Nature Reviews Cancer 13: 883–892.

Aktipis CA, Boddy AM, Jansen G, et al. (2015) Cancer across the tree of life: cooperation and cheating in multicellularity. Philosophical Transactions of the Royal Society, B: Biological Sciences 370: 20140219.

Archetti M, Ferraro DA and Christofori G (2015) Heterogeneity for IGF‐II production maintained by public goods dynamics in neuroendocrine pancreatic cancer. Proceedings of the National Academy of Sciences 112: 1833–1838.

Arnal A, Ujvari B, Crespi B, et al. (2015) Evolutionary perspective of cancer: myth, metaphors, and reality. Evolutionary Applications 8: 541–544.

Axelrod R, Axelrod DE and Pienta KJ (2006) Evolution of cooperation among tumor cells. Proceedings of the National Academy of Sciences 103: 13474–13479.

Bell D, Berchuck A, Birrer M, et al. (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474: 609–615.

Bissell MJ and Hines WC (2011) Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nature Medicine 17: 320–329.

Cairns J (1975) Mutation selection and the natural history of cancer. Nature 255: 1–4.

Caulin AF and Maley CC (2011) Peto's Paradox: evolution's prescription for cancer prevention. Trends in Ecology & Evolution 26: 175–182.

Chen J, Sprouffske K, Huang Q and Maley CC (2011) Solving the puzzle of metastasis: the evolution of cell migration in neoplasms. PLoS One 6: 1–11.

Daoust SP, Fahrig L, Martin AE and Thomas F (2013) From forest and agro‐ecosystems to the microecosystems of the human body: what can landscape ecology tell us about tumor growth, metastasis, and treatment options? Evolutionary Applications 6: 82–91.

Datta RS, Gutteridge A, Swanton C, Maley CC and Graham TA (2012) Modelling the evolution of genetic instability during tumour progression. Evolutionary Applications 6: 20–33.

Dyer MA and Bremner R (2005) The search for the retinoblastoma cell of origin. Nature Reviews Cancer 5: 91–101.

Fialkow P, Jacobson RJ and Papayannopoulou T (1977) Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. The American Journal of Medicine 63: 125–130.

Gatenby RA, Silva AS, Gillies RJ and Frieden BR (2009) Adaptive therapy. Cancer Research 69: 4894–4903.

Germain PL (2012) Cancer cells and adaptive explanations. Biology and Philosophy 27: 785–810.

Greaves M (2010) Cancer stem cells: Back to Darwin? Seminars in Cancer Biology 20: 65–70.

Greaves M (2012) Cancer stem cells as “units of selection.”. Evolutionary Applications 6: 102–108.

Greaves M and Maley CC (2012) Clonal evolution in cancer. Nature 481: 306–313.

Hanahan D and Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144: 646–674.

Hawkins CE, Baars C, Hesterman H, et al. (2006) Emerging disease and population decline of an island endemic, the Tasmanian devil Sarcophilus harrisii. Biological Conservation 131: 307–324.

Hochberg ME, Thomas F, Assenat E and Hibner U (2012) Preventive evolutionary medicine of cancers. Evolutionary Applications 6: 134–143.

Kim R, Emi M and Tanabe K (2007) Cancer immunoediting from immune surveillance to immune escape. Immunology 121: 1–14.

Lee HO, Silva AS, Concilio S, et al. (2011) Evolution of tumor invasiveness: the adaptive tumor microenvironment landscape model. Cancer Research 71: 6327–6337.

Lewontin RC (1970) The units of selection. Annual Review of Ecology and Systematics 1: 1–18.

Maenhaut C, Dumont JE, Roger PP and van Staveren WCG (2010) Cancer stem cells: a reality, a myth, a fuzzy concept or a misnomer? An analysis. Carcinogenesis 31: 149–158.

Maley CC, Galipeau PC, Finley JC, et al. (2006) Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nature Genetics 38: 468–473.

Marco DE, Cannas SE, Montemurro MA, Hu B and Cheng S (2009) Comparable ecological dynamics underlie early cancer invasion and species dispersal, involving self‐organizing processes. Journal of Theoretical Biology 256: 65–75.

McCallum H, Tompkins DM, Jones M, et al. (2007) Distribution and impacts of Tasmanian Devil Facial Tumor Disease. EcoHealth 4: 318–325.

Merlo LMF, Pepper JW, Reid BJ and Maley CC (2006) Cancer as an evolutionary and ecological process. Nature Reviews Cancer 6: 197–200.

Negrini S, Gorgoulis VG and Halazonetis TD (2010) Genomic instability–an evolving hallmark of cancer. Nature Reviews Molecular Cell Biology 11: 220–228.

Nowell P (1976) The clonal evolution of tumor cell populations. Science 194: 23–28.

Okasha S (2006) Evolution and the Levels of Selection. Oxford: Oxford University Press.

Park SY, Gönen M, Kim HJ, Michor F and Polyak K (2010) Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. The Journal of Clinical Investigation 120: 636–644.

Pienta KJ, McGregor N, Axelrod R and Axelrod DE (2008) Ecological therapy for cancer: defining tumors using an ecosystem paradigm suggests new opportunities for novel cancer treatments. Translational Oncology 1: 158–164.

Ryan JJ, Dows BL, Kirk MV, et al. (2010) A systems biology approach to invasive behavior: comparing cancer metastasis and suburban sprawl development. BMC Research Notes 3: 1–13.

Smith JM and Szathmáry E (1995) The Major Transitions in Evolution. Oxford: Oxford University Press.

Spencer SL, Gerety RA, Pienta KJ and Forrest S (2006) Modeling somatic evolution in tumorigenesis. PLoS Computational Biology 2: 0001–0009.

Teng MWL, Swann JB, Koebel CM, Schreiber RD and Smyth MJ (2008) Immune‐mediated dormancy: an equilibrium with cancer. Journal of Leukocyte Biology 84: 988–993.

Wood HM, Conway C, Daly C, et al. (2015) The clonal relationships between pre‐cancer and cancer revealed by ultra‐deep sequencing. Journal of Pathology 237: 296–306.

Wu X and Lippman SM (2011) An intermittent approach for cancer chemoprevention. Nature Reviews Cancer 11: 879–885.

Yates LR and Campbell PJ (2012) Evolution of the cancer genome. Nature Reviews Genetics 13: 795–806.

Further Reading

Attolini CS and Michor F (2009) Evolutionary theory of cancer. Annals of the New York Academy of Sciences 1168: 23–51.

Crespi B and Summers K (2005) Evolutionary biology of cancer. Trends in Ecology & Evolution 20 (10): 545–552.

Lean C and Plutynski A (2016) The evolution of failure: explaining cancer as an evolutionary process. Biology and Philosophy 31: 39–57.

Merlo LM and Maley CC (2010) The role of genetic diversity in cancer. The Journal of Clinical Investigation 120: 401–403.

Thomas F, Fisher D, Fort P, et al. (2012) Applying ecological and evolutionary theory to cancer: a long and winding road. Evolutionary Applications 6 (1): 1–10.

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Wu, Joseph H(Apr 2016) Cancer Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026593]