While metabolic approaches to addressing cancer are not new in the scientific literature or clinical application, they have yet to become part of the Standard of Care in Oncology.
As such, almost a century ago, famed biochemist Otto Warburg postulated a theory where all cancer cells arise from mitochondrial defects in number, structure and function, making them avid consumers of glucose and other fermentable sources, such as glutamine, even in the presence of oxygen.
Despite the ample genetic and histological heterogeneity of cancer, a relatively small number of metabolic processes is responsible for maintaining ATP generation and redox balance.
ATP can only be physically generated in two distinct processes: substrate-level phosphorylation or fueling the proton gradient of the mitochondrial electron transport chain. Their adequate functioning is essential for the maintenance of a proliferative status, redox balance and cell viability.
Notably, contemplating glycolytic capacity as a survival advantage and, at the same time, a vulnerably due to defective mitochondria are two opposing concepts.
Hence, exploiting this known phenomenon via chronic downregulation of glucose via the precise administration of grams of Fat, grams of Protein and grams of Carbohydrates, in combination with intermittent inhibition of glutaminolysis via pan-glutamic inhibitors such as 6-Diazo-5-Oxo-L-Norluecine, can constitute a sustainable and non-toxic method for managing disease.
Therefore, metabolic therapy constitutes a promising management strategy for cancers with very poor prognosis and ineffective Standard of Care. Glycolytic and glutaminolytic dependencies are a well described and targetable feature of many tumors, such as brain, pancreatic, breast, lung, gastric, skin, and prostate, among others. Multiple interventions are viable under the metabolic therapy umbrella, e.g., calorically and macronutrient-controlled nutrition, hyperbaric oxygen therapy, and metabolic reprogramming- however, clinical standardization is required.
