The DOI matches its Crossref record; 112 of the 112 references it cites were found in a registry or an index.
Hypoxia, DNA repair and genetic instability
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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“Furthermore, hypoxia downregulates DNA repair gene expression, and hypoxia/reoxygenation cycles can induce DNA strand breaks and oxidative base damage, gene amplifications, and DNA over-replication (Bristow & Hill, 2008).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Bristow & Hill, 2008
In the citing paper
“Intratumoral hypoxia promotes genomic instability, another hallmark of most cancers (Bristow & Hill, 2008).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Bristow & Hill, 2008
In the citing paper
“These molecular mechanisms become particularly critical in injured or hypoxic tissues, where de novo synthesis is compromised and the salvage pathway is the predominant source of nucleotide precursors for DNA synthesis [78].”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [78]
Citations
Cites
1 retracted
Lysyl oxidase is essential for hypoxia-induced metastasis
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RetractedTargeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
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Hypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177
Exploiting tumour hypoxia in cancer treatment
Brown, J. M., & Wilson, W. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1367 · Cited by 2,828
Drug penetration in solid tumours
Minchinton, A. I., & Tannock, I. F. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1893 · Cited by 2,805
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
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Hypoxia in cancer: significance and impact on clinical outcome
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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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The DNA-damage response in human biology and disease
Jackson, S. P., & Bartek, J. (2009) · Nature · doi:10.1038/nature08467 · Cited by 6,092
Regulation of cancer cell metabolism
Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744
Targeting hypoxia in cancer therapy
Wilson, W. R., & Hay, M. P. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3064 · Cited by 3,172
Role of hypoxia in cancer therapy by regulating the tumor microenvironment
Jing, X., Yang, F., Shao, C., Wei, K., Xie, M., Shen, H., & Shu, Y. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1089-9 · Cited by 2,054
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Chen, Z., Han, F., Du, Y., Shi, H., & Zhou, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01332-8 · Cited by 1,612
Metadata
- Authors
- Bristow, R. G., & Hill, R. P.
- Affiliations
- University Health Network (CA)
- Corresponding author
- Bristow, Robert G.
- Venue
- Nature Reviews Cancer
- Published
- 2008-03
- Volume
- 8
- Issue
- 3
- Pages
- 180-192
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- 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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