Hypoxia inducible factor-1: a novel target for cancer therapy

Anticancer Drugs. 2005 Oct;16(9):901-9. doi: 10.1097/01.cad.0000180116.85912.69.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Benzopyrans / pharmacology
  • Cell Hypoxia / drug effects
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Hypoxia-Inducible Factor 1 / antagonists & inhibitors*
  • Hypoxia-Inducible Factor 1 / physiology
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Models, Biological
  • Mustard Compounds / pharmacology
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / physiopathology
  • Phenylpropionates / pharmacology
  • Phosphoinositide-3 Kinase Inhibitors
  • Signal Transduction / drug effects
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacology
  • Topotecan / pharmacology
  • Topotecan / therapeutic use
  • Tubulin Modulators / pharmacology
  • Tubulin Modulators / therapeutic use

Substances

  • 103D5R
  • 2-amino-3-(4'-N,N-bis(2-chloroethyl)amino)phenylpropionic acid N-oxide
  • Benzopyrans
  • Heterocyclic Compounds, 4 or More Rings
  • Hypoxia-Inducible Factor 1
  • Mustard Compounds
  • Phenylpropionates
  • Phosphoinositide-3 Kinase Inhibitors
  • Tubulin Modulators
  • Topotecan
  • pleurotin
  • Sirolimus