Tumor Hypoxia as a Modifier of DNA Strand Break and Cross-Link Repair

Author(s): Norman Chan, Cameron J. Koch, Robert G. Bristow.

Journal Name: Current Molecular Medicine

Volume 9 , Issue 4 , 2009

Become EABM
Become Reviewer

Abstract:

Hypoxia is a common characteristic of many solid tumors and is associated with poor prognosis. Cells with low oxygen levels can have altered sensitivity to radiotherapy and chemotherapy secondary to changes in the incidence of DNA single- and double-strand breaks (DNA-ssb, DNA-dsb), DNA base damage, DNA-DNA cross-links and DNA-protein cross-links. Recent evidence also supports that cells exposed to chronic hypoxia have a decreased capacity of DNA-dsb repair. This review will examine the influence of shortterm and prolonged hypoxia on the two major pathways of DNA-dsb repair: homologous recombination (HR) and non-homologous end-joining (NHEJ). Novel treatment strategies designed to exploit the hypoxic tumor microenvironment are also discussed. Modification of DNA damage sensing and repair due to fluctuating oxygen levels within a dynamic tumor microenvironment may have profound implications for tumor progression and treatment.

Keywords: DNA repair, hypoxia, OER, radiosensitivity, chemosensitivity, homologous recombination, bioreductive drugs, PARP inhibitors

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 9
ISSUE: 4
Year: 2009
Page: [401 - 410]
Pages: 10
DOI: 10.2174/156652409788167050
Price: $58

Article Metrics

PDF: 14