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

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1056-1062
Number of pages7
JournalBritish Journal of Cancer
Volume109
Issue number4
DOIs
StatePublished - Aug 20 2013

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Evolutionary game theory of growth factor production: Implications for tumour heterogeneity and resistance to therapies'. Together they form a unique fingerprint.

Cite this