Neoplasms are highly dependent on glucose as their substrate for energy production and are generally not able to catabolize other fuel sources such as ketones and fatty acids. Thus, removing access to glucose has the potential to starve cancer cells and induce apoptosis. Unfortunately, other body tissues are also dependent on glucose for energy under normal conditions. However, in human starvation (or in the setting of diet-induced ketogenesis), the body "keto-adapts" and glucose requirements of most tissues drop to almost nil. Exceptions include the central nervous system (CNS) and various other tissues which have a small but obligatory requirement of glucose. Our hypothesized treatment takes keto-adaptation as a prerequisite. We then propose the induction of severe hypoglycemia by depressing gluconeogenesis while administering glucose to the brain. Although severe hypoglycemia normally produces adverse effects such as seizure and coma, it is relatively safe following keto-adaptation. We hypothesize that our therapeutic hypoglycemia treatment has potential to rapidly induce tumor cell necrosis.
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