Critical transitions in a game theoretic model of tumour metabolism

Tumour proliferation is promoted by an intratumoral metabolic symbiosis in which lactate from stromal cells fuels energy generation in the oxygenated domain of the tumour. Furthermore, empirical data show that tumour cells adopt an intermediate metabolic state between lactate respiration and glycolysis. This study models the metabolic symbiosis in the tumour through the formalism of evolutionary game theory. Our game model of metabolic symbiosis in cancer considers two types of tumour cells, hypoxic and oxygenated, while glucose and lactate are considered as the two main sources of energy within the tumour. The model confirms the presence of multiple intermediate stable states and hybrid energy strategies in the tumour. It predicts that nonlinear interaction between two subpopulations leads to tumour metabolic critical transitions and that tumours can obtain different intermediate states between glycolysis and respiration which can be regulated by the genomic mutation rate. The model can apply in the epithelial–stromal metabolic decoupling therapy.