|Cooperation between oxygen-poor cells (red)|
and oxygen-rich ones (green). Source.
Tumors are ecosystems that are composed of different types of cell populations. They can reprogram their metabolism and cooperate with each other. For example, oxygenated cells can use the metabolic by-products produced by oxygen-starved (technical term: hypoxic) cells during metabolism. Hypoxic cells use glucose to produce energy with a compound called lactate as a by-product; lactate can then be used by oxygenated cells to produce far more energy. This process is called metabolic coupling. In this way, the two cell populations cooperate with each other to keep the cancer alive and thriving.
In evolutionary game theory, strategies are being used by different populations, with the outcome being decided by natural selection. It is not required that the players make rational decisions (like in economic game theory), but only that they have a strategy - which is determined by the presence of genes that influence behavior. Evolution tests how good the strategy is in the presence of alternative strategies. The authors used the ideas behind evolutionary game theory to look at the interaction between tumor cell types. In the case of a tumor, strategic decisions are based on the utilization of energy resources in handling nutrient and oxygen availability. In that case, a cell can be considered an agent that responds to changing environmental conditions by changing its strategy based on the energy sources it has available.
So what does this all mean? Well, while they have not identified a time frame during which tumor cells are most vulnerable, they have shown that there is a stage at which tumor cell metabolism can be effectively targeted. During this stage, treatments that focus on reducing the levels or activity of LDH or other important proteins in lactate signaling, uptake, or metabolism could be quite successful. Breaking the metabolic coupling in tumor cells may have therapeutic benefits.