Tumor metabolic reprogramming

Tumor metabolic reprogramming refers to the orchestrated alterations in nutrient uptake and metabolic pathways that cancer cells utilize to support rapid proliferation, survival, and metastasis (Hanahan & Weinberg, 2011 [1]). A hallmark of this process is the Warburg effect, where cancer cells prefer aerobic glycolysis over oxidative phosphorylation even in the presence of oxygen (Vander Heiden et al., 2009 [3]). This reprogramming also involves increased glutaminolysis, lipid synthesis, and pentose phosphate pathway activity to provide building blocks for biomass and maintain redox balance (Pavlova & Thompson, 2016 [2]). While not a single target, various enzymes and transporters within these pathways, such as Hexokinase 2 or Glutaminase, serve as specific therapeutic vulnerabilities (Stine et al., 2015 [4]). Targeting these metabolic shifts aims to starve cancer cells or disrupt their protective mechanisms, though metabolic plasticity often presents a challenge for sustained efficacy (Faubert et al., 2020 [5]). Drugs like Ivosidenib and Enasidenib have successfully targeted specific metabolic mutations in clinical settings, demonstrating the potential of this therapeutic strategy (NIH/NCI, 2018 [6]).

Other names

Warburg effectCancer metabolismMetabolic rewiringMetabolic adaptation in cancerOncometabolism

Inhibition of specific metabolic enzymes (e.g., IDH1/2, glutaminase, hexokinase) or transporters (e.g., MCT1) to disrupt the supply of energy and biosynthetic precursors required for tumor growth and survival (Stine et al., 2015 [4]).