It is a longstanding debate whether
cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most of (if not all) the hallmarks of
cancer could be the consequence of the Warburg's effect. As a result of the metabolic impairment of the oxidative phosphorylation, there is a decrease in
ATP concentration. To compensate the reduced energy yield, there is massive
glucose uptake, anaerobic glycolysis, with an up-regulation of the Pentose Phosphate Pathway resulting in increased biosynthesis leading to increased cell division and local pressure. This increased pressure is responsible for the fractal shape of the
tumor, the secretion of
collagen by the fibroblasts and plays a critical role in metastatic spread. The massive extrusion of
lactic acid contributes to the extracellular acidity and the activation of the immune system. The decreased oxidative phosphorylation leads to impairment in CO2 levels inside and outside the cell, with increased intracellular
alkalosis and contribution of
carbonic acid to extracellular
acidosis-mediated by at least two
cancer-associated
carbonic anhydrase isoforms. The increased intracellular
alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Mitochondrial disappearance (such as seen in very aggressive
tumors) is a consequence of mitochondrial swelling, itself a result of decreased
ATP concentration. The transmembrane pumps, which extrude, from the mitochondria,
ions, and water, are
ATP-dependant.
Therapy aiming at increasing both the number and the efficacy of mitochondria could be very useful.