HIF repressors under chronic hypoxia

Decreased ability in oxygen delivery and diffusion of the blood vessels and increased oxygen consumption in the rapidly proliferating cancer cells both contribute to reduced oxygen availability in the solid tumors, a major signature of the tumor microenvironment [1]. The oxygen concentration is dynamically changed within the tumor, and thus tumor cells are frequently subjected to acute or chronic hypoxia. Tumor cells exposed to chronic hypoxia are highly malignant and resistant to radiation therapy and chemotherapy [1]. Hypoxia-inducible factor 1 (HIF-1) and HIF-2 are two master regulators in response to low oxygen and mediate tumor progression by regulating the transcription of target genes [2]. HIF-mediated cellular processes are distinct under conditions of acute and chronic hypoxia, which may have great impact on therapeutic consequences.