Targeting hypoxia tolerance in cancer

Drug Resist Updat. 2004 Feb;7(1):25-40. doi: 10.1016/j.drup.2003.12.004.


Regulation of tissue oxygen homeostasis is critical for cell function, proliferation and survival. Evidence for this continues to accumulate along with our understanding of the complex oxygen-sensing pathways present within cells. Several pathophysiological disorders are associated with a loss in oxygen homeostasis, including heart disease, stroke, and cancer. The microenvironment of tumors in particular is very oxygen heterogeneous, which may explain much of our difficulty in treating cancer effectively. This is true when comparing levels of hypoxia among different patient tumors, but also within individual tumors. Accumulating evidence implicates the biological responses to hypoxia and the alterations in these pathways in cancer as important contributors to overall malignancy and treatment efficacy. This has recently prompted several investigations into the possibility of targeting treatment at the biological responses to hypoxia.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins* / drug effects
  • DNA-Binding Proteins* / metabolism
  • DNA-Binding Proteins* / physiology
  • Drug Tolerance
  • Homeostasis
  • Humans
  • Hypoxia* / drug therapy
  • Hypoxia* / metabolism
  • Hypoxia* / physiopathology
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Nuclear Proteins* / drug effects
  • Nuclear Proteins* / metabolism
  • Nuclear Proteins* / physiology
  • Oxygen Consumption*
  • Transcription Factors*


  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Transcription Factors