City Research Online

Abstract

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.

Publication Type:	Article
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Publisher Keywords:	Stackelberg evolutionary games, Evolutionary cancer therapy, Evolutionary game theory, Resistance, Heterogeneity, Mathematical oncology
Subjects:	Q Science > QA Mathematics R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Departments:	School of Science & Technology School of Science & Technology > Mathematics
SWORD Depositor:	Symplectic Administrator

Export

Downloads