Abstract
Heterogeneity in strategies for survival and propagation among the cells that constitute a tumour is a driving force behind the evolution of resistance to cancer treatment. The rules mapping the tumour’s strategy distribution to the fitness of individual strategies can be represented as an evolutionary game. We develop a game assay to measure this property in co-culures of alectinib-sensitive and alectinibresistant non-small cell lung cancer. The games are not only quantitatively different between different environments, but targeted therapy and cancer associated fibroblasts qualitatively switch the type of game being played from Leader to Deadlock. This provides the first empirical confirmation of a central theoretical postulate of evolutionary game theory in oncology: we can treat not just the player, but also the game. Although we concentrate on measuring games played by cancer cells, the measurement methodology we develop can be used to advance the study of games in other microscopic systems.