Multi-dimensional roles of ketone bodies in cancer biology: Opportunities for cancer therapy

Ketone bodies are traditionally viewed as metabolic substrates in carbohydrate restriction and are applied in the treatment of epilepsy and other neurodegenerative diseases. Recently, people have paid more attention to its application in the treatment for cancers. Compared to normal cells, cancer cells maintain a higher level of reactive oxygen species (ROS) due to the dysfunctional oxidative phosphorylation and they highly rely on glucose for glycolysis and pentose phosphate pathway (PPP) to against the oxidative stress. Based on tumor metabolism, ketogenic diets (low-carbohydrate, high-fat, and moderate protein) or ketone supplementation, as non-toxic therapeutic approaches, showed a positive therapeutic advantage in a broad range of malignancies. This review summarizes the multi-dimensional roles of ketone bodies in cancer biology and discusses the potential underlying mechanism in the inhibition of tumor growth.