Evidence for a novel, effective approach to targeting carcinoma catabolism exploiting the first-in-class, anti-cancer mitochondrial drug, CPI-613.

ABSTRACT: Clinical targeting of the altered metabolism of tumor cells has long been considered an attractive hypothetical approach. However, this strategy has yet to perform well clinically. Metabolic redundancy is among the limitations on effectiveness of many approaches, engendering intrinsic single-agent resistance or efficient evolution of such resistance. We describe new studies of the multi-target, tumor-preferential inhibition of the mitochondrial tricarboxylic acid (TCA) cycle by the first-in-class drug CPI-613® (devimistat). By suppressing the TCA hub, indispensable to many metabolic pathways, CPI-613 substantially reduces the effective redundancy of tumor catabolism. This TCA cycle suppression also engenders an apparently homeostatic accelerated, inefficient consumption of nutrient stores

SUBMITTER: Guardado Rivas MO 

PROVIDER: S-EPMC9176802 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature