Microenvironmental control of gene expression: implications for tumor angiogenesis, progression, and metastasis

Semin Radiat Oncol. 1998 Jul;8(3):208-16. doi: 10.1016/s1053-4296(98)80046-5.


Low oxygen tension (hypoxia) is an important prognostic factor in cancer treatment because it affects tumor formation and malignant progression. Many genes governing these complex processes have been found to be oxygen regulated. This article reviews the present knowledge of hypoxia-inducible gene expression and how this affects angiogenesis, progression, and metastasis. Of particular importance are hypoxia-regulated transcription factors because they can modulate expression of countless different genes. Additional genes analyzed in some detail include those encoding angiogenic growth factors, factors controlling blood flow, and those involved in metastasis. Although hypoxia is generally perceived as a hindrance to cancer therapy, it is possibly exploitable because severe oxygen deficiency is tumor specific. Strategies aimed at using the presence of hypoxia in solid tumors include oxygen sensitive chemotherapy and gene therapy.

Publication types

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

MeSH terms

  • Angiogenesis Inducing Agents / genetics
  • Antineoplastic Agents / therapeutic use
  • Cell Hypoxia / genetics
  • Disease Progression
  • Endothelial Growth Factors / genetics
  • Gene Expression Regulation, Neoplastic*
  • Genetic Therapy
  • Humans
  • Lymphokines / genetics
  • Neoplasm Metastasis / genetics*
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / therapy
  • Neovascularization, Pathologic / genetics*
  • Nitric Oxide Synthase / genetics
  • Oxygen Consumption / genetics
  • Prognosis
  • Regional Blood Flow / genetics
  • Transcription Factors / genetics
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Angiogenesis Inducing Agents
  • Antineoplastic Agents
  • Endothelial Growth Factors
  • Lymphokines
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Nitric Oxide Synthase