We analyze the stability of a game-theoretic model of a polymorphic eco-evolutionary system in the presence of human intervention. The goal is to understand how the intensity of this human intervention and competition within the system impact its stability, with cancer treatment as a case study. In this case study, the physician applies anti-cancer treatment, while cancer, consisting of treatment-sensitive and treatment-resistant cancer cells, responds by evolving more or less treatment-induced resistance, according to Darwinian evolution. We analyze how the existence and stability of the cancer eco-evolutionary equilibria depend on the treatment dose and rate of competition between cancer cells of the two different types. We also identify initial conditions for which the resistance grows unbounded. In addition, we adopt the level-set method to find viscosity solutions of the corresponding Hamilton–Jacobi equation to estimate the basins of attraction of the found eco-evolutionary equilibria and simulate typical eco-evolutionary dynamics of cancer within and outside these estimated basins. While we illustrate our results on the cancer treatment case study, they can be generalized to any situation where a human aims at containing, eradicating, or saving Darwinian systems, such as in managing antimicrobial resistance, fisheries management, and pest management. The obtained results help our understanding of the impact of human interventions and intraspecific competition on the possibility of containing, eradicating, or saving evolving species. This will help us with our ability to control such systems.

We present a game-theoretic model of a polymorphic cancer cell population where the treatment-induced resistance is a quantitative evolving trait. When stabilization of the tumor burden is possible, we expand the model into a Stackelberg evolutionary game, where the physician is the leader and the cancer cells are followers. The physician chooses a treatment dose to maximize an objective function that is a proxy of the patient’s quality of life. In response, the cancer cells evolve a resistance level that maximizes their proliferation and survival. Assuming that cancer is in its ecological equilibrium, we compare the outcomes of three different treatment strategies: giving the maximum tolerable dose throughout, corresponding to the standard of care for most metastatic cancers, an ecologically enlightened therapy, where the physician anticipates the short-run, ecological response of cancer cells to their treatment, but not the evolution of resistance to treatment, and an evolutionarily enlightened therapy, where the physician anticipates both ecological and evolutionary consequences of the treatment. Of the three therapeutic strategies, the evolutionarily enlightened therapy leads to the highest values of the objective function, the lowest treatment dose, and the lowest treatment-induced resistance. Conversely, in our model, the maximum tolerable dose leads to the worst values of the objective function, the highest treatment dose, and the highest treatment-induced resistance.