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Thermodynamic Modeling of the Competition Between Cancer and Normal Cells

Abstract One of the recognized differences between normal and cancer cells is in their metabolic profile. Tumor cells tend to produce energy through glycolysis rather than the much more efficient oxidative phosphorylation pathway, which healthy cells generally prefer. This phenomenon is identified as the Warburg effect. Although several functional explanations have been proposed for the Warburg effect, the competitive advantage of it is still subject of debate. Here we present a thermodynamic model to simulate the competition of cancer and normal cells in terms of bioenergetics. Our model shows that the Warburg effect has an advantage because the entropy production rate is increased and metabolic efficiency is decreased for cancer cells. Although inefficiency is generally considered a competitive disadvantage for living organisms, the thermodynamic model shows that it is not always the case. Indeed, when the energy resources are abundant and the system has a limited ability to export entropy, the organism with a higher rate of entropy production will have a higher chance of survival despite its lower metabolic efficiency. This thermodynamic model predicts that as long as there are enough nutrients in circulating blood, there are two thermodynamic strategies to control cancer cell populations, i. e., (i) decreasing the entropy production rate of cancer cells and (ii) increasing normal cells’ entropy production rate.