Understanding the Pathogenesis of Cancer as Metabolic Remodulations

Cancer is a highly cell growing and proliferating pathological condition that hijacks cellular metabolism to fulfill its needs. In the early 1920's the Nobel laureate, Otto H. Warburg, defined aerobic glycolysis as the sine-qua-none characteristic feature of cancer cells. Lately, we are gaining awareness that the characteristic intratumoral heterogeneity is just like a reflectionofintratumoral metabolic diversity. The metabolic phenotype of cancer stem cells (CSCs) differs from that of differentiated cancer cells. Therefrom, the metabolic needs of cancer cells vary within a tumor. In fact, the overflow of glycolytic intermediates isreoriented toward alternative pathways. The pivotal interplay between the glycolytic pathway and other metabolic pathways prevails. Cancer metabolism ensures adequate energy supply, biomass production for rapid growth, prevents oxidative stress, epigenetic modulations, and immune assaults in a hostile tumor microenvironment. Warburg effect has long been considered as an insult to mitochondrial functions, especially the energetically more fruitful oxidative phosphorylation. Current understanding of cancer metabolic and signaling pathways hasshown that mitochondrial functions do exist in cancer cells, but rather their metabolic functions are reprogrammed to favor rapid growth, proliferation, and less ROS production. Herein, we do revise the undersides of the Warburg effect and the metabolic shift of mitochondria with its associated signaling pathways.