Introduction
Temozolomide (TMZ) is part of the standard of care for treatingIntroduction: Temozolomide (TMZ) is part of the standard of care for treatingglioblastoma multiforme (GBM), an aggressive primary brain tumor. New approachesare needed to enhance therapeutic efficacy and reduce toxicity. GBM tumor cells aredependent on glucose and glutamine while relying heavily on aerobic fermentation forenergymetabolism. Restricted availability of glucose and glutaminemay therefore reducedisease progression. Calorically restricted ketogenic diets (KD-R), which reduce glucoseand elevate ketone bodies, offer a promising alternative in targeting energy metabolismbecause cancer cells cannot effectively burn ketones due to defects in the number,structure, and function of mitochondria. Similarly, oxaloacetate, which participates in thedeamination of glutamate, has the potential to reduce the negative effects of excessglutamate found in many brain tumors, while hyperbaric oxygen therapy can reverse thehypoxic phenotype of tumors and reduce growth. We hypothesize that the combinatorialtherapy of KD-R, hyperbaric oxygen, and oxaloacetate, could reduce or eliminate theneed for TMZ in GBM patients.
