Inhibitors of hypoxia-inducible factor-1 signaling.
Hypoxia is a universal feature of solid tumors that arises as the tumor mass outgrows stromal vascular supply. Hypoxia-inducible factor (HIF)-1, a transcription factor upregulated in hypoxia, orchestrates a range of adaptive responses that allow tumor cells to survive oxygen deprivation. Important information regarding the role of HIF-1 in tumor biology was gained from tumor biopsy studies in which HIF-1 expression was strongly associated with poor patient prognosis, and from animal studies in which genetic ablation of HIF-1 signaling retarded tumor growth. These findings motivated an intensive search for small-molecule inhibitors of the HIF-1 pathway. This review describes the progress toward the identification of specific inhibitors of HIF-1, and discuss the first examples of HIF-1-targeted therapeutics to enter clinical development.
Belozerov
Vladimir E
VE
Emory University, Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery, Winship Cancer Institute, 1365C Clifton Road, Atlanta, GA 30322, USA.
Van Meir
Erwin G
EG
D000818:Animals; D018450:Disease Progression; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*
D051793:Hypoxia-Inducible Factor 1