Abstract
Tumors are heterogeneous, evolving ecosystems, composed of sub-populations of neoplastic cells that follow distinct strategies for survival and propagation. The success of a strategy defining any single neoplastic sub-population is dependent on the distribution of other strategies, and on various components of the tumour microenvironment like cancer associated fibroblasts (CAFs). The rules mapping the population's strategy distribution to the fitness of individual strategies can be represented as an evolutionary game. In four different environments, we measure the games between treatment naive (Alectinib therapy sensitive) cells and a derivative line in which resistance was previously evolved. We find that the games are not only qualitatively different between different environments, but that targeted therapy and the presence of CAFs qualitatively switch the type of game being played. This provides the first empirical confirmation for the theoretical postulate of evolutionary game theory (EGT) in mathematical oncology that 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.
