Metabolism-Based Molecular Subtyping Endows Effective Ketogenic Therapy in p53-Mutant Colon Cancer.

ABSTRACT: Although targeting cancer metabolism is a promising therapeutic strategy, clinical success depends on accurate molecular and metabolic subtyping. Here, this study reports two metabolism-based molecular subtypes associated with the ketogenic treatment of colon cancer: glycolytic (glycolysis⁺ /ketolysis^- ) and ketolytic (glycolysis⁺ /ketolysis⁺ ), which are manifested by distinct profiles of metabolic enzymes and mitochondrial dysfunction, and by different responses to ketone-containing interventions in vitro and in vivo. Notably, the glycolytic subtype is able to be transformed into the ketolytic subtype in p53-mutated tumors upon glucose limitation, rendering resistance to ketogenic therapy associated with upregulation of ketolytic enzymes, such

SUBMITTER: Tang M 

PROVIDER: S-EPMC9561794 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature