Evolutionary foundations for cancer biology

Abstract

New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles-cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations-provide a foundation for understanding, preventing, and treating cancer.

Keywords: darwinian; ecological; evolutionary medicine; mismatch; neoplastic; vulnerability.

Figure 1

Evolution explains why cancer exists and also why it is not more common. (A) Cancer results from somatic selection at the cell level that favors neoplastic cells (red) over normal somatic cells (tan). (B) Cancer suppression results from selection at the organism level, favoring organisms that have traits (e.g., DNA repair, cell cycle checkpoints/apoptosis, and certain tissue architectures), which keep neoplastic cells in check (blue) while those individuals with traits that make them susceptible (pink) decrease in prevalence in the population.

Figure 2

Intra-tumor heterogeneity increases the likelihood that some mutants will have a proliferation or survival advantage, resulting in faster progression. Heterogeneity also increases the likelihood that there will be a resistant mutant already present in the cell populations before therapy, making therapeutic resistance and relapse more likely.

Figure 3

The ecological context of cancer cells parallels the ecological context for organisms. Similarities include dependence on limited resources, dependence on neighbors for survival and reproduction, interactions with other species and threats from predation. In the case of cancer cells, their ecological context is characterized by dependence resource delivery from blood vessels, growth and survival signals from neighbors, interactions with microbial species and predation from the immune system. Similarly, the ecological context for organisms is characterized by dependent on resource delivery from the environment, dependence on neighbors for effective survival and reproduction, interactions with other species and threats from predators.