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Games 2018, 9(2), 32; https://doi.org/10.3390/g9020032

Game Theory of Tumor–Stroma Interactions in Multiple Myeloma: Effect of Nonlinear Benefits

1
Department of Electrical and Computer Engineering, University of Kashan, Kashan 8731753153, Iran
2
Department of Electrical and Computer Engineering, Isfahan University of Technology, Isfahan 8415683111, Iran
3
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
*
Authors to whom correspondence should be addressed.
Received: 4 April 2018 / Revised: 18 May 2018 / Accepted: 22 May 2018 / Published: 28 May 2018
(This article belongs to the Special Issue Game Theory and Cancer)
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Abstract

Cancer cells and stromal cells often exchange growth factors with paracrine effects that promote cell growth: a form of cooperation that can be studied by evolutionary game theory. Previous models have assumed that interactions between cells are pairwise or that the benefit of a growth factor is a linear function of its concentration. Diffusible factors, however, affect multiple cells and generally have nonlinear effects, and these differences are known to have important consequences for evolutionary dynamics. Here, we study tumor–stroma paracrine signaling using a model with multiplayer collective interactions in which growth factors have nonlinear effects. We use multiple myeloma as an example, modelling interactions between malignant plasma cells, osteoblasts, and osteoclasts. Nonlinear benefits can lead to results not observed in linear models, including internal mixed stable equilibria and cyclical dynamics. Models with linear effects, therefore, do not lead to a meaningful characterization of the dynamics of tumor–stroma interactions. To understand the dynamics and the effect of therapies it is necessary to estimate the shape of the benefit functions experimentally and parametrize models based on these functions. View Full-Text
Keywords: game theory; cancer; stroma; tumor microenvironment; nonlinear benefits game theory; cancer; stroma; tumor microenvironment; nonlinear benefits
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Sartakhti, J.S.; Manshaei, M.H.; Archetti, M. Game Theory of Tumor–Stroma Interactions in Multiple Myeloma: Effect of Nonlinear Benefits. Games 2018, 9, 32.

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