Evolution of phenotypic plasticity leads to tumor heterogeneity with implications for therapy
Fig 4
Emerging heterogeneity and treatment responses depend on death rate and switch threshold as predicted by mean-field theory.
(A) Average switch parameter κ in the cell population. We can distinguish three different regimes. (1) If there is no cell death, the population is dominated by cells that can invade the surrounding tissue the fastest, which are cells with a switch parameter at zero or slightly below. (2) For a low switch threshold and non-zero death rate, the tumor is dominated by cells with an attractive go-or-grow strategy (κ > 0). However, there is considerable genetic heterogeneity, with repulsive cells at the tumor front, see Fig 3, second column. (3) With increasing switch threshold θ and death rate δ, there is a transition to the repulsive regime, where all cells in the tumor use the repulsive strategy (κ < 0). This transition can be predicted by mean-field theory (black dashed line, given by Eqs 6 and 7. (B) The phenotypic heterogeneity is largest near the transition line between evolutionary regimes. (C) The genetic heterogeneity shows a bimodal behavior, with a minimum at the transition line surrounded by local maxima. (D) The recurrence time is longest in regime (2) and minimal near the transition line as well as for low values of the switch threshold θ.