TY - JOUR T1 - Cancer treatment scheduling and dynamic heterogeneity in social dilemmas of tumour acidity and vasculature JF - bioRxiv DO - 10.1101/067488 SP - 067488 AU - Artem Kaznatcheev AU - Robert Vander Velde AU - Jacob G. Scott AU - David Basanta Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/08/02/067488.abstract N2 - Background Tumours are diverse ecosystems with persistent heterogeneity in various cancer hallmarks like self-sufficiency of growth factor production for angiogenesis and reprogramming of energy-metabolism for aerobic glycolysis. This heterogeneity has consequences for diagnosis, treatment, and disease progression.Methods We introduce the double goods game to study the dynamics of these traits using evolutionary game theory. We model glycolytic acid production as a public good for all tumour cells and oxygen from vascularization via VEGF production as a club good benefiting non-glycolytic tumour cells. This results in three viable phenotypic strategies: glycolytic, angiogenic, and aerobic non-angiogenic.Results We classify the dynamics into three qualitatively distinct regimes: (1) fully glycolytic, (2) fully angiogenic, or (3) polyclonal in all three cell types. The third regime allows for dynamic heterogeneity even with linear goods, something that was not possible in prior public good models that considered glycolysis or growth-factor production in isolation.Conclusion The cyclic dynamics of the polyclonal regime stress the importance of timing for antiglycolysis treatments like lonidamine. The existence of qualitatively different dynamic regimes highlights the order effects of treatments. In particular, we consider the potential of vascular renormalization as a neoadjuvant therapy before follow up with interventions like buffer therapy. ER -