In 1924, Otto Warburg noticed something strange about cancer cells. They consume enormous amounts of glucose but don't use oxygen to break it down efficiently the way healthy cells do. They burn sugar fast, extract very little energy from each molecule, and dump the leftover as lactate. It looks wasteful. It looks counterproductive. And yet every aggressive cancer does it. What follows is a hypothesis. This paper proposes that the Warburg effect is not reprogramming. It is damage: specific, cumulative, structural damage to the machinery that extracts energy from sugar. The machinery keeps running, but it can't do the efficient job anymore. So the cell falls back to the wasteful path because it's the only one still functional. Tumor blood vessels grow chaotically and disorganized, so blood flow through any given region of the tumor is unstable. Oxygen arrives, then doesn't, then arrives again, over and over, minutes to hours apart. Healthy tissue almost never experiences this. Tumor tissue experiences it constantly. This is the same kind of damage that happens during a heart attack or a stroke. When blood flow stops and then comes back, the rush of returning oxygen causes a burst of injury to the tissue (not from the lack of oxygen, but from its return). Cardiologists call this ischemia-reperfusion injury. In a heart attack it happens once, violently, and the heart has to recover. In a tumor it happens over and over, quietly, for years.
Andrew Hooks (Thu,) studied this question.