Cancer Cells' Achilles Heel Possibly Revealed by 'Game Theory'

Cancer is no game, but researchers from Johns Hopkins University are applying the idea of "game theory" to learn how cells cooperate within a tumor to gather energy - possibly revealing the ideal moment to stop metastatic cancer cells in their tracks.

"The reality is that we still can't cure metastatic cancer that has spread from its primary organ and game theory adds to our efforts to attack the problem," lead researcher Kenneth J. Pienta, a university professor of urology, said in a statement.

Game theory is a mathematical study of strategic decision-making often used to predict conflict between individuals or nations, but it is also applied to forecasting cell-to-cell interactions in biology. Tumors contain a variety of cells shifting between cooperative-like to competitive-like states, noted Ardeshir Kianercy, a postdoctoral researcher in Pienta's lab.

"To study tumor cells in isolation is not enough," he said. "It makes sense to study their behavior and relationship with other cells and how they co-evolve together."

Scientists used mathematical and computer tools to set up game parameters based on biological interactions between two types of tumor cells - one oxygen-rich and the other oxygen-poor. Cells within a tumor engage in different types of energy metabolism depending on how close they are to an oxygen-rich blood supply. For instance, tumors in oxygen-poor areas use the sugar glucose whereas those in oxygen-rich areas use lactate.

Both types of tumors work as partners when metastasizing, but their relationship is always changing as the cells mutate. The mutation rate influences the strength of the energy partnerships between the oxygen-rich and oxygen-poor cells and levels of glucose and lactate production and uptake, according to the scientists.

By applying the game theory, researchers found that within certain ranges of mutation rates, "there are critical transitions when a tumor suddenly switches between different types of energy metabolic strategies," Kianercy explained.

This switch may be the small window scientists are looking for during which time cancer cells are most vulnerable to anti-cancer drugs.

It isn't clear yet whether this type of metabolic cooperation occurs in all tumors, but a game theory model is a positive step in the right direction, giving scientists a new way to understand how cancers may progress and how best to undermine its spread in the body.

The findings were described in the journal Interface Focus.