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Cancer cells and adaptive explanations

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A Commentary to this article was published on 08 December 2016

Abstract

The aim of this paper is to assess the relevance of somatic evolution by natural selection to our understanding of cancer development. I do so in two steps. In the first part of the paper, I ask to what extent cancer cells meet the formal requirements for evolution by natural selection, relying on Godfrey-Smith’s (Darwinian populations and natural selection. Oxford University Press, Oxford, 2009) framework of Darwinian populations. I argue that although they meet the minimal requirements for natural selection, cancer cells are not paradigmatic Darwinian populations. In the second part of the paper, I examine the most important examples of adaptation in cancer cells. I argue that they are not significant accumulations of evolutionary changes, and that as a consequence natural selection plays a lesser role in their explanation. Their explanation, I argue, is best sought in the previously existing wiring of the healthy cells.

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Notes

  1. By speaking of cancer development, I explicitly wish to avoid discussions of cancer in light of the evolution of multicellular life (Frank 2007; Frank et al. 2003; Leroi et al. 2003; Buss 1987). What I am interested in is the evolution of cancer cells within a given tumour. This also means that I exclude the very special cases of transmittable cancers (see for instance Belov 2012).

  2. Rather than a simple gradient of more or less Darwinian populations, the multi-dimensionality suggests that there are different kinds of Darwinian processes. Godfrey-Smith (2009) does not explore this in depth, and neither will I do so here.

  3. These stem cells divide asymmetrically to produce an identical daughter (so that the stem cell pool persists) and a progenitor cell (which proliferates very quickly but only up to a certain point). Grompe (2012) provides a short but enlightening review of tissue stem cells and their technical implications.

  4. In fact, many authors have suggested that tissue architecture is an adaptation against cancer (Frank and Nowak 2004; Frank et al. 2003).

  5. B-cells are systematically cited as the exception to this rule, but it must be noted that the list of “exceptions” is beginning to grow at a disturbing pace. See for instance the work of Gage's lab on LINE-1 retrotransposons, most importantly in the central nervous system (Singer et al. 2010).

  6. Proponents of the CSC model argue that heterogeneity and bad prognosis are both consequences of a common cause: the cancer stem cells being blocked early in the differentiation tree. The less differentiated they are, the more their progeny can differentiate heterogeneously, and the greater their capacity for self-renewal (hence the severity of the cancer). However, the two explanations are not aimed at the same kind of heterogeneity. The evolutionary explanation explains the relevance of genetic heterogeneity, while the CSC model is aimed at phenotypic heterogeneity – an heterogeneity that is the consequence of varied differentiation rather than mutation.

  7. For a discussion of this issue, see Shibata's (2006) comment on the results presented by Maley et al. (2006).

  8. It should be immediately obvious that different traits or regions of the fitness landscape will be continuous to different degrees. There will be areas that are more “rugged” than others. Different features of a population might fare differently with respect to dimension C, and hence might be expected to evolve at different rates and to different extents. In principle, this does not prevent us from assessing C for the whole landscape, although in practice this is beyond reach. What it does mean, however, is that this dimension could be of use in a more fine-grained analysis.

  9. For a philosophical discussion of this issue, see Bertolaso 2011.

  10. As Godfrey-Smith acknowledges, the notion of intrinsicality is philosophically very problematic. I believe it is not the best way to make sense of this dimension. Wholly external fitness differences can lead to evolution by natural selection (see for instance Bouchard 2008), and a better way to understand the dimension would be in terms of the stability of the fitness differences over lineages. However, as the full elaboration and defence of this account is beyond the scope of this paper, I will here keep to Godfrey-Smith's characterization of the dimension. I therefore assume that in most cases, the dependence of fitness differences on intrinsic characters is a reliable proxy for the stability of the differences.

  11. Since some years later Karl Illmensee fraudulently reported the cloning of mice (see Kolata 1999), one should be careful in interpreting the results of Mintz and Illmensee's (1975). Hochedlinger et al. (2004) were able to obtain viable chimeric mice by transplanting the nucleus of melanoma cells into oocytes, but these mice showed a very high cancer susceptibility.

  12. For the sake of simplicity, in what follows I make the reasonable assumption that each locus was, throughout the evolution of fresh-water sticklebacks, modified respectively through one mutational event. Should it turn out to be different, it would only make the case stronger.

  13. By cycle or iteration, I do not mean a single generation or reproductive event: rather, it can encompass rounds of natural selection up to the fixation of a variant.

  14. Of course, it would have been historically unthinkable to discover the importance of p53 mutations in this way, but this is altogether another question.

  15. A recent report also suggests that the stroma commonly confers an “innate resistance” – see Straussman et al. (2012).

  16. While there are cases in which all changes appeared together in a single event of massive mutation (Stephens et al. 2011), they are arguably very rare.

  17. Likewise, Huang's (2011) model of unused attractor states offers an equally satisfying explanation.

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Acknowledgments

I am particularly indebted to Mark A. Bedau and Fridolin Groß, who offered very precious assistance in this project, as well as to an anonymous reviewer who was particularly helpful. In addition, I would like to thank all those who took the time to read and comment any of the countless drafts of this paper: Giuseppe Testa, Michel Morange, Pierre-Olivier Méthot, Giovanni Boniolo, Marcel Weber, Lorenzo Del Savio, Annette Kappeler, Marco Annoni, Cecilia Nardini and Matteo Mamelli. Finally, I owe to the European School of Molecular Medicine (SEMM), the IFOM-IEO Campus and the FOLSATEC program the chance to have delved deeper into this science.

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  1. Università degli Studi di Milano, European Institute of Oncology (IEO), Via Adamello 16, 20139, Milan, Italy

    Pierre-Luc Germain

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A comment to this article is available at http://dx.doi.org/10.1007/s10539-016-9555-x.

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Germain, PL. Cancer cells and adaptive explanations. Biol Philos 27, 785–810 (2012). https://doi.org/10.1007/s10539-012-9334-2

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