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

Javad Salimi Sartakhti (), Mohammad Hossein Manshaei () and Marco Archetti ()
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Javad Salimi Sartakhti: Department of Electrical and Computer Engineering, University of Kashan, Kashan 8731753153, Iran
Mohammad Hossein Manshaei: Department of Electrical and Computer Engineering, Isfahan University of Technology, Isfahan 8415683111, Iran
Marco Archetti: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK

Games, 2018, vol. 9, issue 2, 1-11

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.

Keywords: game theory; cancer; stroma; tumor microenvironment; nonlinear benefits (search for similar items in EconPapers)
JEL-codes: C C7 C70 C71 C72 C73 (search for similar items in EconPapers)
Date: 2018
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Handle: RePEc:gam:jgames:v:9:y:2018:i:2:p:32-:d:149268