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Review
. 2017 Feb 1;7(2):a029652.
doi: 10.1101/cshperspect.a029652.

Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks

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Free PMC article
Review

Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks

Angelo Fortunato et al. Cold Spring Harb Perspect Med. .
Free PMC article

Abstract

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection and adaptation or by other evolutionary processes such as founder effects and drift. In cancer biology, as in organismal evolutionary biology, there is controversy about this question and also about the use of adaptation through natural selection as a guiding framework for research. In this review, we discuss the differences and similarities between evolution among somatic cells versus evolution among organisms. We review what is known about the parameters and rate of evolution in neoplasms, as well as evidence for adaptation. We conclude that adaptation is a useful framework that accurately explains the defining characteristics of cancer. Further, convergent evolution through natural selection provides the only satisfying explanation both for how a group of diverse pathologies have enough in common to usefully share the descriptive label of "cancer" and for why this convergent condition becomes life-threatening.

Figures

Figure 1.
Figure 1.
An example of convergent evolution in two species of cave fish descended from different ancestral populations. Amblyopsis rosae (top), and Astyanax mexicanus (bottom). Cave fish live in freshwater caves and have adapted to these specialized niches. Although these are different species, they have independently evolved similar phenotypes, such as loss of pigmentation and eyesight. (Images are under public domain, creative commons license.)
Figure 2.
Figure 2.
Although tumors do not converge genetically, all typically converge on the same “hallmark” phenotypic traits. Here, we use a fitness landscape to illustrate convergent evolution of tumor phenotypes. The x- and y-axes (horizontal dimensions) represent two different quantitative traits (trait A and trait B), and the z-axis (vertical dimension) represents fitness. Fitness increases vertically and also scales in color from light blue (low fitness) to red (high fitness). We show two different neoplasms starting from different phenotypic states, depicted by the black and blue circles in the blue landscape valley. As neoplastic progression advances, these two tumors may follow different trajectories (indicated by the dotted lines) up the fitness peak. However, both tumors will converge on the same malignant phenotype (red fitness peak) showing the hallmarks of cancer.
Figure 3.
Figure 3.
A schematic illustration of a phylogeny for somatic evolution in neoplastic cells over time (x-axis), starting from tumor initiation (far left). Neoplastic cell lineages accumulate somatic mutations during progression and eventually transformation to malignancy (far right). As described in the text, there may be multiple mechanisms of somatic evolution. Before malignancy, cell lineages may evolve by natural selection, in which certain clones have a fitness advantage. However, after transformation to malignancy, some neoplasms may evolve neutrally, in which clonal expansion is rapid (called the “big bang”) (Sottoriva et al. 2015), and most adaptation to the niche of the “endogenous parasite” is already completed.

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