The Ecology of Collective Cancer Invasion: An Evolutionary Game Theory Model

Cancer is an evolutionary disease which exhibits genomic and phenotypic heterogeneity. Together with the tumor microenvironments, the cell subclones within the a tumor form a complex multi-cellular ecosystem. Tumors compromise a variety of specialized phenotypical subclones adapted to various ecological conditions, which influence the response to treatments and prognosis of the diseases. Recent experiments revealed two distinct phenotypes, leaders and followers, in non-small cell lung cancer during collective invasion. We adopt an evolutionary game theory framework to model the cancer microenvironments and the interactions between leader and follower cells. Measuring the total tumor burden and the leader fraction that drive collective invasion, we show that the pairwise interactions between leader and follower cells could alter the collective dynamics. These findings suggest potential new treatment strategies, targeting leader-follower cells interactions. Combinations treatments could reduce tumor burden as well as lower the risk for invasion.