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            <title xml:lang="en">Why the tumor cell metabolism is not that abnormal</title>
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              <p>The cell energy metabolism is a multifactorial and evolving process that we address with a theoretical approach in order to decipher the functioning of the core system of the glycolysis-OXPHOS relationship. The model is based on some key experimental observations and well established facts. It emphasizes the role of lactate as a substrate, as well as the central role of pyruvate in the regulation of the metabolism. The simulations show how imposed environmental constraints and imposed energy requirements push the cell to adapt its metabolism to sustain its needs. The results highlight the cooperativeness of the two metabolic modes and allows to revisit the notions of metabolic switch and metabolic reprogramming. Our results thus tend to show that the Warburg eect is not an inherent characteristic of the tumor cell, but a spontaneous and transitory adaptation mechanism to a disturbed environment. This means that the tumor cell metabolism is not fundamentally dierent from that of a normal cell. This has implications on the way therapies are being considered. The quest to normalize the tumor acidity could be a good strategy.</p>
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