Evolutionary game theory of growth factor production: implications for tumour heterogeneity and resistance to therapies

Archetti, M (2013) Evolutionary game theory of growth factor production: implications for tumour heterogeneity and resistance to therapies. British Journal of Cancer, 109 (4). pp. 1056-1062. ISSN 0007-0920

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    Abstract

    Background: Tumour heterogeneity is documented for many characters, including the production of growth factors, one of the hallmarks of cancer. What maintains heterogeneity remains an open question that has implications for diagnosis and treatment, as drugs that target growth factors are susceptible to the evolution of resistance. Methods: I use evolutionary game theory to model collective interactions between cancer cells, to analyse the dynamics of the production of growth factors and the effect of therapies that reduce their amount. Results: Five types of dynamics are possible, including the coexistence of producer and non-producer cells, depending on the production cost of the growth factor, on its diffusion range and on the degree of synergy of the benefit it confers to the cells. Perturbations of the equilibrium mimicking therapies that target growth factors are effective in reducing the amount of growth factor in the long term only if the reduction is extremely efficient and immediate. Conclusion: Collective interactions within the tumour can maintain heterogeneity for the production of growth factors and explain why therapies like anti-angiogenic drugs and RNA interference that reduce the amount of available growth factors are effective in the short term but often lead to relapse. Alternative strategies for evolutionarily stable treatments are discussed.

    Item Type: Article
    Faculty \ School: Faculty of Science > School of Biological Sciences
    University of East Anglia > Faculty of Science > Research Groups > Organisms and the Environment
    Depositing User: Pure Connector
    Date Deposited: 20 Aug 2013 06:29
    Last Modified: 25 Jul 2018 08:32
    URI: https://ueaeprints.uea.ac.uk/id/eprint/43137
    DOI: 10.1038/bjc.2013.336

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