Cancer Evolution


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