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

J. S. Sartakhti,M. Manshaei,M. Archetti

Published 2018 in Games

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.

PUBLICATION RECORD

  • Publication year

    2018

  • Venue

    Games

  • Publication date

    2018-05-28

  • Fields of study

    Medicine, Mathematics, Computer Science

  • Identifiers
    DOI 10.3390/G9020032
  • External record

    Open on Semantic Scholar

  • Source metadata

    Semantic Scholar

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