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.
Alhatem et al. (Wed,) studied this question.