Genetically-defined metabolic reprogramming in cancer

Oncogenes and tumor suppressors regulate cell metabolism. Evidence demonstrates that tumorigenic mutations in these genes tend to orchestrate metabolic activity into a platform that promotes cell survival, growth, and proliferation. Recent work has shown that some metabolic enzymes are also mutated in cancer, and that these mutations may influence malignancy directly. Thus, these enzymes seem to function as oncogenes and tumor suppressors, and would appear to be compelling targets for therapeutic intervention. Here, we review several enzymes mutated in cancer – phosphoglycerate dehydrogenase, isocitrate dehydrogenases 1 and 2, succinate dehydrogenase, and fumarate hydratase – and discuss exciting new work that has begun to pull back the curtain on how mutations in these enzymes influence tumorigenesis.