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Phys Biol. 2011 Feb;8(1):015016. doi: 10.1088/1478-3975/8/1/015016. Epub 2011 Feb 7.

The role of IDH1 mutated tumour cells in secondary glioblastomas: an evolutionary game theoretical view.

Author information

1
Integrated Mathematical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. david.basanta@kclalumni.net

Abstract

Recent advances in clinical medicine have elucidated two significantly different subtypes of glioblastoma which carry very different prognoses, both defined by mutations in isocitrate dehydrogenase-1 (IDH-1). The mechanistic consequences of this mutation have not yet been fully clarified, with conflicting opinions existing in the literature; however, IDH-1 mutation may be used as a surrogate marker to distinguish between primary and secondary glioblastoma multiforme (sGBM) from malignant progression of a lower grade glioma. We develop a mathematical model of IDH-1 mutated secondary glioblastoma using evolutionary game theory to investigate the interactions between four different phenotypic populations within the tumor: autonomous growth, invasive, glycolytic, and the hybrid invasive/glycolytic cells. Our model recapitulates glioblastoma behavior well and is able to reproduce two recent experimental findings, as well as make novel predictions concerning the rate of invasive growth as a function of vascularity, and fluctuations in the proportions of phenotypic populations that a glioblastoma will experience under different microenvironmental constraints.

PMID:
21301070
PMCID:
PMC3166886
DOI:
10.1088/1478-3975/8/1/015016
[Indexed for MEDLINE]
Free PMC Article

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