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The evolution of failure: explaining cancer as an evolutionary process

A Commentary to this article was published on 08 December 2016

“Through failure we understand design.” Frank, 2007.

Abstract

One of the major developments in cancer research in recent years has been the construction of models that treat cancer as a cellular population subject to natural selection. We expand on this idea, drawing upon multilevel selection theory. Cancer is best understood in our view from a multilevel perspective, as both a by-product of selection at other levels of organization, and as subject to selection (and drift) at several levels of organization. Cancer is a by-product in two senses. First, cancer cells co-opt signaling pathways that are otherwise adaptive at the organismic level. Second, cancer is also a by-product of features distinctive to the metazoan lineage: cellular plasticity and modularity. Applying the multilevel perspective in this way permits one to explain transitions in complexity and individuality in cancer progression. Our argument is a reply to Germain’s (2012) scepticism towards the explanatory relevance of natural selection for cancer. The extent to which cancer fulfills the conditions for being a paradigmatic Darwinian population depends on the scale of analysis, and the details of the purported selective scenario. Taking a multilevel perspective clarifies some of the complexities surrounding how to best understand the relevance of evolutionary thinking in cancer progression.

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Notes

  1. For a history of evolutionary perspectives on cancer, see, Morange (2012).

  2. A reviewer asks whether the lineage of cells in a clonal population is a “population.” We grant that it is an atypical population, in that the population is all descended from a clone. But, if clonal populations of bacteria such as Lenski’s E. coli are populations, we don’t see why clonal populations in a tumor would not be.

  3. A ‘r’ selection population is one with a high growth rate, seeding many individuals. ‘R’ selection is often associated with populations which gain from dispersing over hostile environments. In contrast ‘k’ selection population have low growth rates due to the population living in an environment near carrying capacity. See Macarthur and Wilson (1967).

  4. A reviewer comments: “There is no denying that the success of metastasis depends on many evolved features and interactions (including cells other than the colonizing cells) and, as the author points out, that features such as heterogeneity are tumor-level property… However, in order to show that tumours have complex adaptations, it is insufficient to show that tumours have developed complex traits, or that these promote progression, and one must also show that these traits were selected at this level, rather than for the benefit of single cells.” This is an excellent comment and central concern worth addressing. In our view, a trait that promotes relative survival and reproductive success of an entity at some level need not be (initially) selected for survival and reproductive success at that particular level. As long as it (currently) promotes survival and reproductive success of entities at that level, the trait is selected for at that level. We believe that we have shown this to be the case, and, the following references provide further elaboration of examples (Gatenby et al. 2007; Gavert and Ben-Ze’ev 2010; Egeblad et al. 2010; Mueller and Fuesnig 2004). Ruling out selection on a given level by arguing that a trait was not initially selected for to benefit that level would rule out all selection on all coopted traits, which would (potentially) rule out a good deal of selection even at the level of individual cells or organisms. See, e.g., Lloyd (2012) for discussion.

  5. In Hanahan and Weinberg (2000) they claim cancer is a population of cells with the following features (1) Self stimulation of growth (2) resist inhibitory signals (3) apoptosis avoidance (4) angiogenesis (5) unlimited replication (6) metastasis.

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Lean, C., Plutynski, A. The evolution of failure: explaining cancer as an evolutionary process. Biol Philos 31, 39–57 (2016). https://doi.org/10.1007/s10539-015-9511-1

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Keywords

  • Cancer
  • Multilevel selection
  • Darwinian populations
  • Tumors
  • By-product of selection