Supplemental ketone metabolic therapy slows tumor growth and increases survival time in mice with metastatic cancer

Metastasis is responsible for 90% of cancer‐related deaths in the U.S. Failure to test therapies in natural pre‐clinical models of metastasis has prevented the effective translation of treatments from lab to clinic. Metastatic cancer cells are highly glycolytic, requiring a large supply of glucose for energy. Mitochondrial dysfunction prevents cancer from efficiently using ketones for energy. Furthermore, ketones inhibit cancer cell proliferation in vitro . The metabolic deficiencies of cancer can be exploited with a ketogenic diet (KD) which lowers glucose and elevates ketones in the blood, a strategy that slows cancer progression in animals and humans. We hypothesized that elevating blood ketones with supplemental ketone administration (SKA) would inhibit cancer progression and enhance efficacy of the KD. We tested this metabolic therapy in the luciferase‐tagged VM‐M3 mouse model of metastatic cancer which spreads naturally in an immunocompetent host, mimicking the natural metastatic phenotype. Mice were fed either ketogenic or standard diet with supplemental ketones (1,3‐butanediol or ketone ester.) Tumor growth was monitored by in vivo bioluminescent imaging. SKA slowed tumor growth and increased survival time by 34–51% when delivered with standard or ketogenic diet. We propose that SKA could enhance the efficacy of standard care and improve the outcome of patients with advanced metastatic disease. Grant Funding Source : Office of Naval Research