title: Hypoxia inducible factor-1: a novel target for cancer therapy.
abstract: Hypoxia develops in the majority of solid tumors due to the inability of the existing vascular system to supply the growing tumor mass with adequate amounts of oxygen. A large body of clinical evidence suggests that intratumoral hypoxia correlates with the elevated aggressive behavior of cancer cells and their resistance to therapy, leading to poor patient prognoses. A heterodimeric transcription factor, hypoxia inducible factor-1 (HIF-1), has been shown to orchestrate a large number of molecular events required for the adaptation of tumor cells to hypoxia. Therefore, HIF-1 has become an attractive target for the development of anti-cancer drugs. Here, we highlight some of the recently developed small-molecule inhibitors of HIF-1 function. These drugs disrupt the HIF-1 signaling pathway through a variety of mechanisms, including the inhibition of HIF-1alpha protein synthesis, stabilization, nuclear translocation and HIF-1 transactivation of target genes.
authors.affiliation: Department of Neurosurgery, Hematology/Oncology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Belozerov
authors.forename: Erwin G
authors.initials: EG
authors.lastname: Van Meir
mesh_terms: D001578:Benzopyrans / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009150:Mustard Compounds / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010666:Phenylpropionates / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D019772:Topotecan / Q000494:pharmacology / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C496879:103D5R; C492908:2-amino-3-(4'-N,N-bis(2-chloroethyl)amino)phenylpropionic acid N-oxide; D001578:Benzopyrans; D006576:Heterocyclic Compounds, 4 or More Rings; D051793:Hypoxia-Inducible Factor 1; D009150:Mustard Compounds; D010666:Phenylpropionates; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050257:Tubulin Modulators; D019772:Topotecan; C479485:pleurotin; D020123:Sirolimus