The role of evolutionary game theory in spatial and non-spatial models of the survival of cooperation in cancer: a review

Evolutionary game theory (EGT) is a branch of mathematics which considers populations of individuals interacting with each other to receive pay-offs. An individual's pay-off is dependent on the strategy of its opponent(s) as well as on its own, and the higher its pay-off, the higher its reproductive fitness. Its offspring generally inherit its interaction strategy, subject to random mutation. Over time, the composition of the population shifts as different strategies spread or are driven extinct. In the last 25 years there has been a flood of interest in applying EGT to cancer modelling, with the aim of explaining how cancerous mutations spread through healthy tissue and how intercellular cooperation persists in tumour-cell populations. This review traces this body of work from theoretical analyses of well-mixed infinite populations through to more realistic spatial models of the development of cooperation between epithelial cells. We also consider work in which EGT has been used to make experimental predictions about the evolution of cancer, and discuss work that remains to be done before EGT can make large-scale contributions to clinical treatment and patient outcomes.