Cancer in Light of Experimental Evolution

Abstract

Cancer initiation, progression, and the emergence of therapeutic resistance are evolutionary phenomena of clonal somatic cell populations. Studies in microbial experimental evolution and the theoretical work inspired by such studies are yielding deep insights into the evolutionary dynamics of clonal populations, yet there has been little explicit consideration of the relevance of this rapidly growing field to cancer biology. Here, we examine how the understanding of mutation, selection, and spatial structure in clonal populations that is emerging from experimental evolution may be applicable to cancer. Along the way, we discuss some significant ways in which cancer differs from the model systems used in experimental evolution. Despite these differences, we argue that enhanced prediction and control of cancer may be possible using ideas developed in the context of experimental evolution, and we point out some prospects for future research at the interface between these traditionally separate areas.

The reverse evolution from multicellularity to unicellularity during carcinogenesis

“…To address this question, we carried out experimental evolution 10,11 of a human breast cell-derived xenograft tumour in mice to characterize the complete evolutionary history of a tumour. Although the micro-environment of the mouse mammary gland is not ideal for studying human breast cancer, such a strategy has long been used in the cancer community 12 , and has been proven to be highly successful in human cancer biology 13 .…”

First principles of Hamiltonian medicine

“…For autosomal genes in humans and other metazoans, levels of relatedness are straightforward products of meiotic links. However, for non-autosomal genes in metazoans, and for microbes or cancer cells, relatedness and inclusive-fitness effects must be conceptualized more carefully, in terms of an allele's effects on replication of copies of itself (strictly, relative to alternative alleles at the locus) in other entities, be they groups of pure or mixed-clone bacterial cells [9], more or less genetically divergent human cells within an individual [79], or interacting humans themselves. Across all of these contexts, Hamilton's rule can also be expanded to include forms of social interaction based on trait-sharing ('kind' selection) and feedback of social trait effects on the actor's fitness ('kith' selection) [161]; this formalization allows the application of Hamilton's rule across an even wider array of situations affecting fitness and health, from genes to groups.…”

“…Transmissible cancers in domestic dogs and Tasmanian devils [78], indeed, represent empirical bridges between infectious disease and carcinogenesis, as does the application of experimental-evolutionary methods [79], and the development of relatively 'evolution-proof' therapeutic agents that delay or preclude the evolution of resistance [80]. Microbes themselves may even be subjected to cancer-like overgrowth by 'rogue lineages' [81], whose control and dynamics should provide insights into repression of over-proliferating cells much more generally [81,82].…”

Human Organisms from an Evolutionary Perspective: Its Significance for Medicine

“…Ultimately, the aim of EM is to provide both conceptual tools and practical insights for medical and public health professionals in their quest for improving the human condition as it relates to health and disease. Although this EM perspective is beginning to gain traction in the scholarly literature (Sprouffke et al 2012;Alexander et al 2014), EM advocates have been strongly urging that medical practitioners and public health officials would do well to consider more diligently evolutionary reflections as they pertain to both PHJs and the nature and modification of health and disease states in human populations.…”