Cited by 1,140Cancer, Hypoxia, and MetabolismDNA Repair MechanismsCell death mechanisms and regulation

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Hypoxia, DNA repair and genetic instability

Bristow, Robert G., Hill, Richard P.·2008·Nature Reviews Cancer

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Abstract

Areas of hypoxic tumour tissue are known to be resistant to treatment and are associated with a poor clinical prognosis. There are several reasons why this might be, including the capacity of hypoxia to drive genomic instability and alter DNA damage repair pathways. Significantly, current models fail to distinguish between the complexities of the hypoxic microenvironment and the biological effects of acute hypoxia exposures versus longer-term, chronic hypoxia exposures on the transcription and translation of proteins involved in genetic stability and cell survival. Acute and chronic hypoxia might lead to different biology within the tumour and this might have a direct effect on the design of new therapies for the treatment of hypoxic tumours.

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“When tissue metabolism exceeds metabolic supply, as is the case for most tumours, the hypoxic response leads to a series of changes in protein expression to protect against cell deat”
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Authors: Bristow, R. G., & Hill, R. P.
Affiliations: University Health Network (CA)
Corresponding author: Bristow, Robert G.
ORCID: Bristow, Robert G.
Hill, Richard P.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2008-03
Volume: 8
Issue: 3
Pages: 180-192
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc2344
OpenAlex: W2012276721
Cited by: 1,140
References: 112
Citations by year: 2026: 29 · 2025: 60 · 2024: 44 · 2023: 51 · 2022: 75 · 2021: 86 · 2020: 70 · 2019: 70 · 2018: 78 · 2017: 66 · 2016: 54 · 2015: 50 · 2014: 63 · 2013: 66 · 2012: 73
FWCI: 4.89
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Funders: National Cancer Institute
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: chronic hypoxia, acute hypoxia, genomic instability, DNA repair, treatment resistance, cancer prognosis, cancer therapy design
MeSH terms: Animals, Hypoxia, DNA Damage, DNA Repair, Humans, Models, Biological, Neoplasm Metastasis, Neoplasms, Phenotype, Transcription, Genetic, Protein Biosynthesis, Gene Expression Regulation, Neoplastic, Disease Progression, Genomic Instability

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