Journal of Molecular Medicine

, Volume 85, Issue 2, pp 139–148

Hypoxia-induced genetic instability—a calculated mechanism underlying tumor progression

  • L. Eric Huang
  • Ranjit S. Bindra
  • Peter M. Glazer
  • Adrian L. Harris
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Abstract

The cause of human cancers is imputed to the genetic alterations at nucleotide and chromosomal levels of ill-fated cells. It has long been recognized that genetic instability—the hallmark of human cancers—is responsible for the cellular changes that confer progressive transformation on cancerous cells. How cancer cells acquire genetic instability, however, is unclear. We propose that tumor development is a result of expansion and progression—two complementary aspects that collaborate with the tumor microenvironment—hypoxia in particular, on genetic alterations through the induction of genetic instability. In this article, we review the recent literature regarding how hypoxia functionally impairs various DNA repair pathways resulting in genetic instability and discuss the biomedical implications in cancer biology and treatment.

Keywords

DNA repair Genetic instability HIF Hypoxia Tumor microenvironment Tumor progression 

Abbreviations

DSB

double-strand break

HIF

hypoxia-inducible factor

HR

homologous recombination

HRE

hypoxia-responsive element

MMR

mismatch repair

NER

nucleotide excision repair

NHEJ

nonhomologous end-joining

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • L. Eric Huang
    • 1
  • Ranjit S. Bindra
    • 2
  • Peter M. Glazer
    • 2
  • Adrian L. Harris
    • 3
  1. 1.Department of NeurosurgeryUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Department of Therapeutic RadiologyYale University School of MedicineNew HavenUSA
  3. 3.Cancer Research UK Growth Factor Group, Weatherall Institute of Molecular MedicineJohn Radcliffe HospitalOxfordUK

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