Cancer as an Evolutionary Process

  • Lília Perfeito
Part of the Learning Materials in Biosciences book series (LMB)


Cancer is the product of natural selection happening within our bodies. Our cells can be seen as individuals in populations, able to mature, reproduce with mutation, and die. All it takes is chance (and external factors such as smoking habits) for the emergence of mutant cells that divide uncontrollably and take over the whole tissue, creating aggressive tumors. If we understand the roots of this process, we will be able to develop better therapies that target the uniqueness of each cancer. In this chapter we will discuss how cancer is modulated both by somatic and germline evolution and we will examine the consequences of interpreting tumor progression as an adaptive process.


  1. 1.
    Milholland B, Dong X, Zhang L, Hao X, Suh Y, Vijg J (2017) Differences between germline and somatic mutation rates in humans and mice. Nat Commun 8:15183. PubMed PMID: 28485371; PubMed Central PMCID:PMC5436103CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Mozos E, Méndez A, Gómez-Villamandos JC, Martín De Las Mulas J, Pérez J (1996) Immunohistochemical characterization of canine transmissible venereal tumor. Vet Pathol 33(3):257–263CrossRefGoogle Scholar
  3. 3.
    Metzger MJ, Villalba A, Carballal MJ, Iglesias D, Sherry J, Reinisch C, Muttray AF, Baldwin SA, Goff SP (2016) Widespread transmission of independent cancer lineages within multiple bivalve species. Nature 534(7609):705–709. Epub 2016 Jun 22. PubMed PMID: 27338791; PubMed Central PMCID: PMC4939143CrossRefGoogle Scholar
  4. 4.
    Peto R (2015) Quantitative implications of the approximate irrelevance of mammalian body size and lifespan to lifelong cancer risk. Philos Trans R Soc Lond Ser B Biol Sci 370(1673):pii: 20150198. PubMed PMID: 26056360; PubMed Central PMCID: PMC4581039CrossRefGoogle Scholar
  5. 5.
    Sulak M, Fong L, Mika K, Chigurupati S, Yon L, Mongan NP, Emes RD, Lynch VJ (2016) TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. elife 5:pii:e11994. CrossRefGoogle Scholar
  6. 6.
    Vazquez JM, Sulak M, Chigurupati S, Lynch VJ (2018) A zombie LIF gene in elephants is upregulated by TP53 to induce apoptosis in response to DNA damage. Cell Rep 24(7):1765–1776. CrossRefGoogle Scholar
  7. 7.
    Fabian D, Flatt T (2011) The evolution of aging. Nat Educ Knowl 3(10):9Google Scholar
  8. 8.
    Ungewitter E, Scrable H (2009) Antagonistic pleiotropy and p53. Mech Ageing Dev 130(1–2):10–17. Epub 2008 Jul 1. Review. PubMed PMID: 18639575; PubMed Central PMCID: PMC2771578CrossRefGoogle Scholar
  9. 9.
    Smith KR, Hanson HA, Hollingshaus MS (2013) BRCA1 and BRCA2 mutations and female fertility. Curr Opin Obstet Gynecol 25(3):207–213. Review. PubMed PMID: 23411475; PubMed Central PMCID: PMC4010322CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Maley CC, Reid BJ (2005) Natural selection in neoplastic progression of Barrett’s esophagus. Semin Cancer Biol 15(6):474–483. ReviewCrossRefGoogle Scholar
  11. 11.
    de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L, Jamal-Hanjani M, Shafi S, Murugaesu N, Rowan AJ, Grönroos E, Muhammad MA, Horswell S, Gerlinger M, Varela I, Jones D, Marshall J, Voet T, Van Loo P, Rassl DM, Rintoul RC, Janes SM, Lee SM, Forster M, Ahmad T, Lawrence D, Falzon M, Capitanio A, Harkins TT, Lee CC, Tom W, Teefe E, Chen SC, Begum S, Rabinowitz A, Phillimore B, Spencer-Dene B, Stamp G, Szallasi Z, Matthews N, Stewart A, Campbell P, Swanton C (2014) Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science 346(6206):251–256. PubMed PMID: 25301630; PubMed Central PMCID: PMC4636050CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Berneburg M, Gattermann N, Stege H, Grewe M, Vogelsang K, Ruzicka T, Krutmann J (1997) Chronically ultraviolet-exposed human skin shows a higher mutation frequency of mitochondrial DNA as compared to unexposed skin and the hematopoietic system. Photochem Photobiol 66(2):271–275CrossRefGoogle Scholar
  13. 13.
    Kibota TT, Lynch M (1996) Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature 381(6584):694–696CrossRefGoogle Scholar
  14. 14.
    Prindle MJ, Fox EJ, Loeb LA (2010) The mutator phenotype in cancer: molecular mechanisms and targeting strategies. Curr Drug Targets 11(10):1296–1303. Review. PubMed PMID: 20840072; PubMed Central PMCID: PMC4073693CrossRefGoogle Scholar
  15. 15.
    Martens EA, Kostadinov R, Maley CC, Hallatschek O (2011) Spatial structure increases the waiting time for cancer. New J Phys 13:pii: 115014. Epub 2011 Nov 28. PubMed PMID: 22707911; PubMed Central PMCID: PMC3375912CrossRefGoogle Scholar
  16. 16.
    Barker N (2014) Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol 15(1):19–33. Epub 2013 Dec 11. ReviewCrossRefGoogle Scholar

Further Reading

  1. Leroi AM, Bartke A, De Benedictis G, Franceschi C, Gartner A, Gonos ES, Fedei ME, Kivisild T, Lee S, Kartaf-Ozer N, Schumacher M, Sikora E, Slagboom E, Tatar M, Yashin AI, Vijg J, Zwaan B (2005) What evidence is there for the existence of individual genes with antagonistic pleiotropic effects? Mech Ageing Dev 126(3):421–429. ReviewCrossRefGoogle Scholar
  2. Lipinski KA, Barber LJ, Davies MN, Ashenden M, Sottoriva A, Gerlinger M (2016) Cancer evolution and the limits of predictability in precision cancer medicine. Trends Cancer 2(1):49–63. Epub 2016 Jan 29. Review. PubMed PMID: 26949746; PubMed Central PMCID: PMC4756277CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Lília Perfeito
    • 1
  1. 1.Instituto Gulbenkian CiênciaOeirasPortugal

Personalised recommendations