Carcinogenesis: – Mutagenic Versus Metabolic Models: An Alternative Hypothesis

Carcinogenesis, while traditionally attributed to the accumulation of driver mutations in genes regulating cell proliferation and apoptosis, may also be explored as a consequence of fundamental metabolic reprogramming, an idea catalyzed by the Warburg effect, where cancer cells exhibit a paradoxical preference for glycolysis over the far more efficient oxi-dative phosphorylation, thereby implying that metabolic dysregulation may be a primary instigator of neoplastic transformation. Proposing an alternative hypothesis, informed by both metabolic dysfunction and evolutionary biology, it becomes apparent that a precipi-tous loss of cellular energy may stimulate an atavistic response, an evolutionarily con-served remnant of ancestral survival mechanisms inherited from unicellular organisms, wherein rapid proliferation and migration were triggered to enhance survival in fluctuat-ing environments, responses that in modern times lead to pathological angiogenesis and unchecked cell growth, thereby bridging the gap between genetic and metabolic models of cancer.