Cancer as an evolutionary and ecological process

Key Points

  • Neoplasms are composed of an ecosystem of evolving clones, competing and cooperating with each other and other cells in their microenvironment, and this has important implications for both neoplastic progression and therapy.

  • Selection at the different levels of genes, cells and organisms might conflict, and have resulted in a legacy of tumour-suppression mechanisms and vulnerability to oncogenesis in our genomes.

  • Most of the dynamics of evolution have not been measured in neoplasms, including mutation rates, fitness effects of mutations, generation times, population structure, the frequency of selective sweeps and the selective effects of our therapies.

  • Many of the genetic and epigenetic alterations observed in neoplasms are evolutionarily neutral.

  • Cancer therapies select for cancer stem cells with resistance mutations, although various evolutionary approaches have been suggested to overcome this problem, including selecting for benign or chemosensitive cells, altering the carrying capacity of the neoplasm and the competitive effects of neoplastic and normal cells on each other.

  • Dispersal theory suggests that high cell mortality and variation of resources and population densities across space might select for metastasis.

  • There is evidence of competition, predation, parasitism and mutualism between co-evolving clones in and around a neoplasm.

  • We will need to interfere with clonal evolution and alter the fitness landscapes of neoplastic cells to prevent or cure cancer. Evolutionary biology should be central to this endeavor.


Neoplasms are microcosms of evolution. Within a neoplasm, a mosaic of mutant cells compete for space and resources, evade predation by the immune system and can even cooperate to disperse and colonize new organs. The evolution of neoplastic cells explains both why we get cancer and why it has been so difficult to cure. The tools of evolutionary biology and ecology are providing new insights into neoplastic progression and the clinical control of cancer.

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Figure 1: Intestinal tissue architecture and sub-population structure.
Figure 2: Asexual evolution in neoplastic progression.
Figure 3: Ecological interactions.
Figure 4: Evolution of a neoplastic population.


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This work was supported by the US National Institutes of Health, the Commonwealth of Pennsylvania, and the Pew Charitable Trust, and initiated by the Santa Fe Institute. We thank W. Ewens, M. Carroll and J. Radich for helpful comments. We apologize to our peers whose work we were unable to cite owing to space limitations.

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Correspondence to Carlo C. Maley.

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A set of cells that share a common genotype owing to descent from a common ancestor. In some contexts a clone is more restrictively defined as a set of genetically identical cells.


The average contribution of a genotype to future generations. Fitness is generally a function of both survival and reproduction.

Genetic drift

Random changes in allele frequencies over generations. This dynamic of random sampling has a greater effect in smaller populations.

Neutral mutation

A mutation that has no fitness effect (survival or reproductive effect).


When an allele (or in this case a clone) reaches 100% frequency in a population.

Hitchhiker mutation

An effectively neutral mutation that expands in a population because it is linked to a selectively advantageous allele. Sometimes called a 'passenger mutation' in cancer biology.

Molecular clock

When mutations occur at a constant rate, the number of mutations that have accumulated between two different lineages is representative of the time since the lineages diverged.

Selective sweep

The process of an adaptive mutation spreading through a population, typically ending in fixation.


An interaction between individuals that decreases the fitness of one party but has no effect on the other.

Lotka–Volterra competition equations

The Lotka–Volterra model of competition is based on logistic growth equations of two populations that negatively affect each other's growth.


An interaction between individuals that increases the fitness of both parties.


An interaction between individuals that increases the fitness of one party and has no fitness effect on the other.

Fitness landscape

A multi-dimensional space in which every point represents the genotype or phenotype of a cell and its fitness value. Points are connected if a mutational event can transform one genotype (or phenotype) into the other.

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Merlo, L., Pepper, J., Reid, B. et al. Cancer as an evolutionary and ecological process. Nat Rev Cancer 6, 924–935 (2006).

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