In May of 2016 we awarded a substantial grant to Dr. Thomas Seyfried's lab at Boston College. The grant is funding the exploration of a cocktail of metabolic therapies in a metastatic mouse model. The experiment will test the combination of the ketogenic diet, glycolytic inhibitors, oxygen therapy, glutamine inhibitors, exogenous ketones, and other metabolic targeting therapies in combination.
The goal is to refine and optimize a metabolic cocktail treatment that can be immediately transferred into the clinic. Research Project Summary The objective of this research proposal is to develop a non-toxic diet/drug therapeutic cocktail that can resolve primary tumor growth and secondary tumor metastatic lesions in a range of preclinical models of cancer. Emerging evidence indicates that cancer is primarily a mitochondrial metabolic disease in line with Warburg’s central hypothesis (1, 2). Respiratory insufficiency, resulting from defects in the number, structure, or function of mitochondria, is the hallmark metabolic malady seen to some degree in the neoplastic cells of all types of cancer (3, 4). Respiratory insufficiency will force cancer cells to rely more heavily on fermentation metabolism than on oxidative phosphorylation for maintaining energy balance. The increased aerobic fermentation seen in many cancer cells has been referred to as the Warburg effect (5). This common metabolic defect in cancer cells offers a therapeutic strategy for disease management through the targeting of those fuels needed to drive fermentation energy. The key question, therefore, is whether malignant and metastatic cancers can be resolved non-toxically using metabolic therapy.