Interview with Dominic D'Agostino, Ph.D

As an Assistant Professor at the University of South Florida since 2008, D’Agostino teaches students of the Morsani College of Medicine and the Department of Molecular Pharmacology and Physiology,

with a focus on such topics as neuropharmacology, medical biochemistry, cell metabolism, and signaling. In his capacities as a researcher, Dominic D’Agostino enjoys support from the Office of Naval Research (ONR), the Department of Defense (DoD), the Alzheimer’s Association, and other entities for investigations into oxygen toxicity, ketogenic diets, cancer, and metabolic/neuroprotective strategies.  His latest work is on hyperbaric oxygen therapy for cancer.  

Question: Do you believe cancer research is largely off-track?

Dr. D'Agostino: Yes, the time, money and resources invested into cancer research are not saving lives and this is a problem largely due to viewing cancer has a disease of genetic origin.   Another problem is that the accepted standard care consisting of cytotoxic chemotherapy and radiation often does more harm than good to the cancer patient.  

Question: Do you believe cancer is a disease of metabolism?

Dr. D'Agostino: Yes, most cancers result from environmental and lifestyle factors that promote cellular stress and progressive mitochondrial damage.  Mitochondrial damage impairs energy metabolism.   The fidelity of the genome is tightly correlated with stable energy (ATP) generation from the mitochondria, and failure to maintain cellular energy triggers the activation of cancer genes.  

Question: How does hyperbaric oxygen therapy affect cancer cells?

Dr. D'Agostino: The direct effect of hyperbaric oxygen on cancer cells is largely unknown, but evidence suggests that cancer cells overproduce reactive oxygen species (ROS) in response to elevated levels of oxygen.  The general consensus is that hyperbaric oxygen can reverse tumor hypoxia, and hypoxia has been shown to drive tumor progression and metastatic processes.  In addition, cancer cells have elevated levels of ROS, but also have a finite capacity to buffer excess ROS production.   Many toxic chemotherapy drugs work by augmenting ROS production, which overwhelms the antioxidant capacity of cancer cells and kills them.  Hyperbaric oxygen is a natural way to kill cancer cells that are selectively vulnerable to hyperoxia-induced oxidative stress.  Our data suggest that hyperbaric oxygen therapy is most effective for treating cancer when used with a metabolic therapy that lowers blood glucose and elevates blood ketone levels.  

Question: What cancer therapies do you think have the most promise?

Dr. D'Agostino: Cancer cells are genetically heterogeneous, but almost all express the same metabolic phenotype, which is lactate production in the presence of oxygen (Warburg effect).    Metabolic therapies like the restricted ketogenic diet exploit the Warburg effect and can be used as a stand-alone therapy or combined with other therapies like hyperbaric oxygen or cancer-specific metabolic inhibitors.  

Question: What avenues of experimentation would you like to see explored with respect to cancer in the future?

Dr. D'Agostino: Therapeutic ketosis and hyperbaric oxygen offer a nontoxic approach to cancer management, especially when combined.  Therapeutic ketosis can be achieved with a ketogenic diet and ketone supplements (ketone ester or ketone salts) and this makes it possible to achieved sustained hypoglycemia because the ketones function as an alternative fuel source.  Normal health cells readily adapt to using fatty acids and ketone bodies for fuel, but cancer cells lack this metabolic flexibility.  Nontoxic metabolic therapies and hyperbaric oxygen therapy exploits the overlapping metabolic and oxidative vulnerability of cancer cells.  Our laboratory is focused on validating this approach to cancer management in pre-clinical studies and moving these nontoxic therapies into the clinic. The 1 cause 1 cure foundation thanks Dr. D'Agostino for his time and efforts.

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