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.
Export Options
About this article
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Compounds Combining Aminoadamantane and Monoterpene Moieties: Cytotoxicity and Mutagenic Effects
Medicinal Chemistry Aflibercept: A Novel VEGF Targeted Agent to Explore the Future Perspectives of Anti-Angiogenic Therapy for the Treatment of Multiple Tumors
Mini-Reviews in Medicinal Chemistry Gene Expression Abnormalities in Thymoma
Current Pharmacogenomics LRRC4 Inhibits Glioma Cell Growth and Invasion Through a miR-185- Dependent Pathway
Current Cancer Drug Targets Therapeutic Trials in Human Transmissible Spongiform Encephalopathies: Recent Advances and Problems to Address
Infectious Disorders - Drug Targets Neuro-endocrine Markers in Neoplasms. Diagnostic Interest and Future Prospects
Current Proteomics Hypoxia-Inducible Factor-1 as Regulator of Angiogenesis in Rheumatoid Arthritis - Therapeutic Implications
Current Medicinal Chemistry Multi-Classifier Based on Hard Instances- New Method for Prediction of Human Immunodeficiency Virus Drug Resistance
Current Topics in Medicinal Chemistry “Smart” Nanocarriers: A New Paradigm for Tumor Targeting Drug Delivery Systems
Drug Delivery Letters Cancer Molecular Imaging: Radionuclide-Based Biomarkers of the Epidermal Growth Factor Receptor (EGFR)
Current Topics in Medicinal Chemistry Opioid-modulating Peptides: Mechanisms of Action
Current Topics in Medicinal Chemistry The Mechanism of Memory Impairment Induced by Aβ Chronic Administration Involves Imbalance between Cytokines and Neurotrophins in the Rat Hippocampus
Current Alzheimer Research Role of the Insulin Receptor Variant Forms in Human Metabolic Disorders
Current Genomics Inhibition of Brain Phospholipase A2 by Antimalarial Drugs: Implications for Neuroprotection in Neurological Disorders
Medicinal Chemistry Reviews - Online (Discontinued) ADP-Ribosyl Cyclase as a Therapeutic Target for Central Nervous System Diseases
Central Nervous System Agents in Medicinal Chemistry The NK-1 Receptor: A New Target in Cancer Therapy
Current Drug Targets Mining Sarcomas by Proteomics Approaches: Ewing Sarcoma on the Spotlight
Recent Patents on Biotechnology Cancer Vaccines: Emphasis on Pediatric Cancers
Current Pharmaceutical Design The Novel Multi-Target Iron Chelator, M30 Modulates HIF-1α-Related Glycolytic Genes and Insulin Signaling Pathway in the Frontal Cortex of APP/PS1 Alzheimer’s Disease Mice
Current Alzheimer Research A Comparative Analysis of Brain and Plasma Aβ Levels in Eight Common Non-Transgenic Mouse Strains: Validation of a Specific Immunoassay for Total Rodent Aβ
Current Alzheimer Research