Recent agents targeting HIF-1α for cancer therapy

J Cell Biochem. 2013 Mar;114(3):498-509. doi: 10.1002/jcb.24390.

Abstract

The discovery of hypoxia-inducible factor-1 (HIF-1) has led to an increasing understanding of the mechanism of tumor hypoxia in the past two decades. As a key transcriptional regulator, HIF-1 plays a central role in the adaptation of tumor cells to hypoxia by activating the transcription of targeting genes, which regulate several biological processes including angiogenesis, cell proliferation, survival, glucose metabolism and migration. The inhibitors of HIF-1 in cancer have provided us a new clue for the targeting cancer therapy. This review will introduce the general knowledge of the biology characteristic of HIF-1 and mechanism of O(2)-dependent regulation. Moreover, a number of chemical inhibitors plus protein and nucleic acid inhibitors are included and classified mainly based on their different mechanism of inhibiting action. We also prefer to discuss the advantages of protein and nucleic acid inhibitors compared with chemical inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Hypoxia
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation, Neoplastic
  • Glucose / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Mixed Function Oxygenases / metabolism
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Protein Kinase Inhibitors / metabolism*
  • Repressor Proteins / metabolism
  • Transcription, Genetic

Substances

  • Antineoplastic Agents
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Protein Kinase Inhibitors
  • Repressor Proteins
  • Mixed Function Oxygenases
  • HIF1AN protein, human
  • Glucose