Hypoxia inducible factor-1: a novel target for cancer therapy.
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.
Belozerov
Vladimir E
VE
Department of Neurosurgery, Hematology/Oncology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Van Meir
Erwin G
EG
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
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