GLUT1 Production in Cancer Cells: A Tragedy of the Commons

The tragedy of the commons, a concept originally developed by economist William Lloyd to describe overgrazing by cattle, is a phenomenon in which individual selfishness in a group setting leads to depletion of a shared resource, to the detriment of the overall population. We hypothesize that such a situation occurs in cancer cells in which cells increase production of membrane GLUT transporters for glucose in the presence of competing cells, obtaining a modest personal gain at a great group cost. To formalize this notion, we create a game-theoretic model for capturing the effects of competition on cancer cell transporter production and nutrient uptake. We show that the production of transporters per cell increases with a logistic trend as the number of competing cells in a microenvironment increase, but nutrient uptake per cell decreases in a power law fashion. By simulating GLUT1 inhibitor and glucose deprivation treatments, we demonstrate a synergistic combination of standard-of-care therapies and clustering of cancer cells, while also displaying the existence of a trade-off between competition among cancer cells and depression of the gain function. Assuming cancer cell transporter production is heritable, we then show the potential for a sucker's gambit technique to be used to counteract this trade-off, thereby allowing one to take advantage of both cellular competition and gain function depression by strategically changing environmental conditions.