HIF-1 inhibitors for cancer therapy: From gene expression to drug discovery

Research output: Contribution to journalReview article

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric protein composed of HIF-1α and HIF-1α subunits, which is activated in response to reduced O2 availability. HIF-1 transactivates genes encoding proteins that are involved in key aspects of the cancer phenotype, including cell immortalization and de-differentiation, stem cell maintenance, genetic instability, glucose uptake and metabolism, pH regulation, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy. Increased HIF-1α levels, as determined by immunohistochemical analysis of tumor biopsy specimens, is associated with increased mortality in many human cancers. Drugs that inhibit HIF-1 activity and have anti-cancer effects in vivo have been identified and clinical trials are warranted to establish the contexts in which addition of such agents to therapy protocols will result in increased patient survival.

Original languageEnglish (US)
Pages (from-to)3839-3843
Number of pages5
JournalCurrent pharmaceutical design
Volume15
Issue number33
DOIs
StatePublished - Nov 1 2009

Keywords

  • Angiogenesis
  • Cancer
  • Chemotherapy
  • Hypoxia-inducible factor
  • Invasion
  • Metastasis
  • Metronomic therapy
  • Oxygen

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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