Evolutionary perspective of cancer: myth, metaphors, and reality

Abstract

The evolutionary perspective of cancer (which origins and dynamics result from evolutionary processes) has gained significant international recognition over the past decade and generated a wave of enthusiasm among researchers. In this context, several authors proposed that insights into evolutionary and adaptation dynamics of cancers can be gained by studying the evolutionary strategies of organisms. Although this reasoning is fundamentally correct, in our opinion, it contains a potential risk of excessive adaptationism, potentially leading to the suggestion of complex adaptations that are unlikely to evolve among cancerous cells. For example, the ability of recognizing related conspecifics and adjusting accordingly behaviors as in certain free-living species appears unlikely in cancer. Indeed, despite their rapid evolutionary rate, malignant cells are under selective pressures for their altered lifestyle for only few decades. In addition, even though cancer cells can theoretically display highly sophisticated adaptive responses, it would be crucial to determine the frequency of their occurrence in patients with cancer, before therapeutic applications can be considered. Scientists who try to explain oncogenesis will need in the future to critically evaluate the metaphorical comparison of selective processes affecting cancerous cells with those affecting organisms. This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications.

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

“…One of the arguments against applying an adaptationist framework to cancer cells is that the scope of resulting adaptation may be limited because the human lifetime is too short for complex cell adaptations to evolve de novo (Arnal et al 2015). In this section, we examine the validity of this claim by reviewing the literature on the pace of evolutionary change in neoplasms.…”

“…Also related to the finite human life span, some investigators have mistakenly argued that the potential for adaptation is limited by the fact that most cancers will die with their host (Davies and Lineweaver 2011; Arnal et al 2015). In fact, this does not preclude adaptations in a neoplasm during the lifetime of the host.…”

“…Evolution of adaptation through natural selection follows as a logical necessity. This is a precise description of the process, not merely a metaphor ( pace Arnal et al 2015). …”

“…In organismal biology, there has long been controversy over the power and limitations of the “adaptationist program” of searching for Darwinian adaptation as a way to generate hypotheses and guide research (Gould and Lewontin 1979; Mayr 1983), and some of this has parallels in cancer biology (Arnal et al 2015). Does somatic evolution produce complex novelties, or merely remove or activate cell functions that are already encoded in the constitutive human genome?…”

“…This is contrasted with a null model of neutral evolution and an approach that emphasizes the importance of constraints and side effects in influencing the evolutionary trajectory (Gould and Lewontin 1979). A similar debate is now present in cancer biology, with some investigators arguing against “excessive adaptationism,” partly on the grounds that a few decades is probably not long enough for cancer cells to evolve all their observed complex traits (Arnal et al 2015). This debate can be summarized by two questions: First, are cancers characterized by natural selection or by neutral evolution?…”