Oncological implications of hypoxia inducible factor-1alpha (HIF-1alpha) expression

Cancer Treat Rev. 2006 Oct;32(6):407-16. doi: 10.1016/j.ctrv.2006.05.003. Epub 2006 Aug 4.

Abstract

Solid tumours contain regions of hypoxia, which may be a prognostic indicator and determinant of malignant progression, metastatic development and chemoradio-resistance. The degree of intra-tumoural hypoxia has been shown to be positively correlated with the expression of the transcription factor hypoxia-inducible factor 1. HIF-1 is composed of 2 sub-units, namely HIF-1alpha and HIF-1beta. The production of hypoxia inducible factor 1-alpha has been identified as a key element in allowing cells to adapt and survive in a hostile hypoxic environment via a variety of pathways. HIF-1alpha is stabilised by hypoxia at the protein level, and also by the oncogenes HER2neu, v-src and ras. There are over 60 target genes for HIF-1, many of which are activated in cancers in comparison to equivalent normal tissues. Chemotherapeutic modulation of HIF-1 pathways has shown promise for patients with chemo-radio resistant or recurrent tumours in Phase II clinical trials. We herein review the existing literature on hypoxia inducible factor-1alpha, particularly its role in carcinogenesis and clinical implications of its over-expression.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Clinical Trials as Topic
  • Humans
  • Hypoxia-Inducible Factor 1*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Hypoxia-Inducible Factor 1