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
Current Molecular Medicine
Title: Tumor Hypoxia as a Modifier of DNA Strand Break and Cross-Link Repair
Volume: 9 Issue: 4
Author(s): Norman Chan, Cameron J. Koch and Robert G. Bristow
Affiliation:
Keywords: DNA repair, hypoxia, OER, radiosensitivity, chemosensitivity, homologous recombination, bioreductive drugs, PARP inhibitors
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.
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Cite this article as:
Chan Norman, Koch J. Cameron and Bristow G. Robert, Tumor Hypoxia as a Modifier of DNA Strand Break and Cross-Link Repair, Current Molecular Medicine 2009; 9 (4) . https://dx.doi.org/10.2174/156652409788167050
DOI https://dx.doi.org/10.2174/156652409788167050 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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