To further understand how to develop anti-metastatic cancer drugs, researchers applied game theory to the biological interactions between cells in a tumor.

They found that tumor cells sometimes switch between metabolic energy strategies. During this switch, the tumor may be vulnerable enough for scientists to disrupt it with anti-cancer drugs and break the cooperative behaviors between the cells within the tumor.

The study was conducted at Johns Hopkins and published in the journal Interface Focus.

"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," says Kenneth J. Pienta, director of the Prostate Cancer Program at Johns Hopkins.

Game theory is a mathematical analysis used to predict cooperation and conflict between entities. In recent research, scientists began using game theory to understand and predict behaviors of interacting cells.

Tumors consist of cells that are sometimes cooperating, sometimes competing. According to Ardeshir Kianercy, a postdoctoral researcher supervised by Pienta, studying the cells individually does not reveal enough information to understand the tumors and their vulnerabilities. They must look at the behaviors and interactions between the tumor cells.

The scientists at Johns Hopkins looked at the interactions between oxygen-rich and oxygen-poor tumor cells. Depending on proximity to oxygen-rich blood, tumor cells use different metabolic strategies. The two kinds of tumor cells generally interact in a cooperative way, with the oxygen-poor cells producing energy via sugar glucose, thus releasing lactate, and the oxygen-rich cells using lactate for metabolism. The latter cells then release more glucose for the oxygen-poor cells in the process.

Tumor cells, however, mutate. The rate of mutation is a strong determining factor in the strength of the relationship between the two kinds of tumor cells as well as the available levels of lactate and glucose.

To figure out when transitions in metabolic strategies occur in tumors, the scientists calculated mutation rates and glucose and lactate levels. They found that the switches in strategy likely occur when tumors progress and spread to other regions. Their findings suggest that, during this window in time, the tumors are vulnerable and attacking the tumors with anti-cancer therapies in this window may be a viable and promising attempt at halting the progress of metastatic cancer.

Metastatic cancer is cancer that has spread from its original region. For example, bone metastatic cancer may start in other regions such as breast, prostate or lungs, and then it spreads to the bones. While treatable for pain, metastatic cancer is thus far incurable.  

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