Game theory identifies the ideal time to disrupt the cooperation of metastatic cancer cells -
no cancer in, but the Johns Hopkins researchers borrow ideas from the evolutionary theory of games to learn how cells cooperate in a tumor to gather energy. Their experiments, they said, could identify the perfect time to disrupt the cooperation of metastatic cancer cells and make a tumor more vulnerable to anticancer drugs.
"The reality is that we can not cure metastatic cancer that has spread to his theory of organ and primary game adds to our efforts to tackle the problem," says Kenneth J. Pienta, MD Donald S. Coffey professor of urology at Johns Hopkins Brady Urological Institute and director of the prostate cancer program at the Johns Hopkins Kimmel cancer Center. A description of the work appears in 1 June 20 report in the journal focus Interface .
Game theory is a mathematical study of strategic decision making, and has been widely used to predict the conflict and cooperation between individuals and even nations, but increasingly is applied to the forecast of cell-cell interactions in biology with an ecological perspective. Tumors contain a variety of cells shift between cooperatives as competitive as the United, said Ardeshir Kianercy, Ph.D., a postdoctoral researcher in the lab of Pienta. "To study the tumor cells in isolation is not enough," he noted. "It makes sense to study their behavior and relationships with other cells and how they co-evolve together."
In their research, the Johns Hopkins scientists use mathematical and computational tools to configure game settings based on biological interactions between the two types of tumor cells, an oxygen-rich and the other poor oxygen. The cells within a tumor are engaged in various types of energy metabolism depending on how close they are to a supply of oxygen-rich blood. Tumor cells in the oxygen poor areas use the sugar glucose to produce energy and, in the process, release a compound called lactate. the oxygen-rich cells use the lactate in a different type of energy metabolism processes and consequently the release of glucose which can be used by poor cell oxygen to burn their own energy.
In general, the process is an effective partnership that can help a tumor to thrive, but the partnership is still evolving tumor cells mutate. mutation rate affect the strength of energy partnerships between cells and the levels of glucose and lactate production and the rich absorption of oxygen and low oxygen, according to scientists.
Application of the calculations of game theory that represented the tumor mutation rates of cells and glucose levels and potential lactate, scientists have found that in certain mutation rate ranges, "there a critical transitions when a tumor suddenly moved between different types of metabolic energy strategies, "said Kianercy. This switch in the playbook of tactics energy production can occur when tumors grew and spread.
Scientists believe that tumors may be particularly vulnerable in this window switching strategy, making it a potentially ideal time for clinicians to disrupt the environment and the wreck of the tumor partnership between its cells.
Some tumor cells, for example, can cause normal cells around them to release lactate for fuel. A therapy that disrupts the transport lactate to tumor cells during a critical transition "could push a tumor to a state where the cells do not cooperate with each other," said Kianercy. "And if they become uncooperative, they are more likely to stay in this state and the tumor may become more vulnerable to anti-cancer therapies."
Pienta said he did not yet know whether this type of metabolic cooperation occurs in all tumors. But the model of game theory used in the study gives scientists a new way to understand how cancers can develop. "We want ultimately to test how we can stop this process with therapies for cancer patients," he said.
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