Cancer, Hypoxia, and Metabolism

Solid tumors frequently outgrow their blood supply, creating oxygen-depleted regions that force cancer cells to rewire how they produce energy and build the molecular components needed for rapid growth. A central player in this adaptation is hypoxia-inducible factor 1 (HIF-1), a transcription factor that orchestrates a broad shift toward glycolysis—even when oxygen is available, a phenomenon known as the Warburg effect—while also reshaping glutamine metabolism and suppressing mitochondrial respiration. Understanding these metabolic shifts matters because they confer survival advantages that drive tumor progression and resistance to therapy, but also expose potential vulnerabilities that could be exploited pharmacologically, particularly through inhibiting key enzymes like hexokinase II or interfering with oxygen-sensing pathways. Active work in the area focuses on disentangling how cancer cells balance competing metabolic demands across spatially heterogeneous tumor environments, and on identifying which metabolic dependencies are most tractable as therapeutic targets without broadly disrupting normal tissue function.

Works

145,448

Total citations

2,970,771

Keywords

HIF-1Warburg EffectTumor HypoxiaCancer Cell MetabolismGlutamine MetabolismOxygen Sensing