Hypoxia-inducible factors in cancer stem cells and inflammation

• Hypoxia-inducible factors maintain cancer stem cells.
• Hypoxia-inducible factors set the cancer microenvironment.
• Genetic and epigenetic mechanisms confer oxygen resistance of hypoxia-inducible factors.
• Hypoxia-inducible factors are targets for therapeutic elimination of cancer stem cells and reprograming of the tumor microenvironment.

Hypoxia-inducible factors (HIF) mediate metabolic switches in cells in hypoxic environments, including those in both normal and malignant tissues with limited supplies of oxygen. Paradoxically, recent studies have shown that cancer stem cells (CSCs) and activated immune effector cells exhibit high HIF activity in normoxic environments and that HIF activity is critical in the maintenance of CSCs as well as the differentiation and function of inflammatory cells. Given that inflammation and CSCs are two major barriers to effective cancer therapy, targeting HIF may provide a new approach to developing such treatments.