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Tumour progression has been described as a sequence of traits or phenotypesthat cells have to acquire if the neoplasm is to become an invasive andmalignant cancer. Although the genetic mutations that lead to these phenotypesare random, the process by which some of these mutations become successful andspread is influenced by the tumour microenvironment and the presence of otherphenotypes. It is thus likely that some phenotypes that are essential in tumourprogression will emerge in the tumour population only with the prior presenceof other different phenotypes. In this paper we use evolutionary game theory toanalyse the interactions between three different tumour cell phenotypes definedby autonomous growth, anaerobic glycolysis, and cancer cell invasion. The modelallows to understand certain specific aspects of glioma progression such as theemergence of diffuse tumour cell invasion in low-grade tumours. We find thatthe invasive phenotype is more likely to evolve after the appearance of theglycolytic phenotype which would explain the ubiquitous presence of invasivegrowth in malignant tumours. The result suggests that therapies which increasethe fitness cost of switching to anaerobic glycolysis might decrease theprobability of the emergence of more invasive phenotypes

Evolutionary game theory elucidates the role of glycolysis in glioma progression and invasion