Mathematical modeling plays an important role in our understanding and targeting therapy resistance mechanisms in cancer. The polymorphic Gompertzian model, analyzed theoretically and numerically by Viossat and Noble to demonstrate the benefits of adaptive therapy in metastatic cancer, describes a heterogeneous cancer population consisting of therapy-sensitive and therapy-resistant cells. In this study, we demonstrate that the polymorphic Gompertzian model successfully captures trends in both in vitro and in vivo data on non-small cell lung cancer (NSCLC) dynamics under treatment. Additionally, for the in vivo data of tumor dynamics in patients undergoing treatment, we compare the goodness of fit of the polymorphic Gompertzian model to that of the classical oncologic models, which were previously identified as the models that fit this data best. We show that the polymorphic Gompertzian model can successfully capture the U-shape trend in tumor size during cancer relapse, which can not be fitted with the classical oncologic models. In general, the polymorphic Gompertzian model corresponds well to both in vitro and in vivo real-world data, suggesting it as a candidate for improving the efficacy of cancer therapy, for example, through evolutionary/adaptive therapies.

Evolutionary game theory mathematically conceptualizes and analyzes biological interactions where one’s fitness not only depends on one’s own traits, but also on the traits of others. Typically, the individuals are not overtly rational and do not select, but rather inherit their traits. Cancer can be framed as such an evolutionary game, as it is composed of cells of heterogeneous types undergoing frequency-dependent selection. In this article, we first summarize existing works where evolutionary game theory has been employed in modeling cancer and improving its treatment. Some of these game-theoretic models suggest how one could anticipate and steer cancer’s eco-evolutionary dynamics into states more desirable for the patient via evolutionary therapies. Such therapies offer great promise for increasing patient survival and decreasing drug toxicity, as demonstrated by some recent studies and clinical trials. We discuss clinical relevance of the existing game-theoretic models of cancer and its treatment, and opportunities for future applications. Moreover, we discuss the developments in cancer biology that are needed to better utilize the full potential of game-theoretic models. Ultimately, we demonstrate that viewing tumors with evolutionary game theory has medically useful implications that can inform and create a lockstep between empirical findings and mathematical modeling. We suggest that cancer progression is an evolutionary competition between different cell types and therefore needs to be viewed as an evolutionary game.