Turning cancer's metabolic plasticity into fragility- an evolving paradigm

ABSTRACTIn an elegant report, Corbet et al1 recently demonstrated the much needed insight to exploit cancer's metabolic reprogramming for potential therapeutic intervention. In brief, the findings underscore the principle that abrogation of mitochondrial pyruvate metabolism upregulates glycolysis, and sensitizes cancer cells to radiation. Distinctive from the conventional approach of inhibition/ down-regulation of glycolysis, this emerging paradigm of forced-upregulation of glycolysis (i.e., a “hyperglycolytic” phenotype) concomitant with a reduced mitochondrial capacity turns the metabolic plasticity into vulnerability that may have implications in therapeutic targeting. Nevertheless, this commendable report1 also provokes scientific curiosity and future directions of research on the opportunities and challenges of such forced upregulation of glycolysis in cancer.