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Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response
Open accessAbstract
Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer therapies, as it compromises treatment and drives malignant progression. This review seeks to clarify the oxygen levels that are pertinent to this issue. It is argued that normoxia (20% oxygen) is an extremely poor comparator for "physoxia", i.e. the much lower levels of oxygen universally found in normal tissues, which averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it should be recognized that the median oxygenation in untreated tumours is significantly much lower, falling between approximately 0.3% and 4.2% oxygen, with most tumours exhibiting median oxygen levels <2%. This is partially dependent on the tissue of origin, and it is notable that many prostate and pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even further, often unrecognized, changes in tumour oxygenation that may vary longitudinally, increasing or decreasing during treatment in ways that are not always predictable. Studies that fail to take cognizance of the actual physiological levels of oxygen in tissues (approximately 5%) and tumours (approximately 1%) may fail to identify the real circumstances driving tumour response to treatment and/or malignant progression. This can be of particular importance in genetic studies in vitro when comparison to human tumours is required.
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“Reduced oxygen tension activates a conserved hypoxic signaling network centered on hypoxia-inducible factors (HIFs)”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [2]
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“Nevertheless, both physiological and pathological states can transiently disrupt the equilibrium between oxygen supply and demand, resulting in tissue and cellular hypoxia”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [2]
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“In liver metastases of colorectal cancer, the median PO2 was 6 mmHg as compared with 30 mmHg in normal liver tissue (20).”
From HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy (2022) · cites this paper as [20]
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“This response features extensive transcriptional reprogramming aimed at preserving cellular integrity under low-oxygen conditions”
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Hypoxia: Friend or Foe for drug delivery in Pancreatic Cancer
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A potential revolution in cancer treatment: A topical review of FLASH radiotherapy
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Metadata
- Authors
- McKeown, S. R.
- Affiliations
- University of Ulster (GB)
- Corresponding author
- McKeown, S R
- Venue
- The British Journal of Radiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-03
- Volume
- 87
- Issue
- 1035
- Pages
- 20130676
- ISSN
- 0007-1285 (ISSN-L)
- 1748-880X
- PMC
- PMC4064601
- OpenAlex
- W2018722597
- Cited by
- 1,050
- References
- 126
- Citations by year
- 2026: 84 · 2025: 122 · 2024: 129 · 2023: 139 · 2022: 137 · 2021: 152 · 2020: 107 · 2019: 68 · 2018: 56 · 2017: 33 · 2016: 13 · 2015: 5 · 2014: 4
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Radiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- tumor hypoxia, tumor oxygenation, normoxia, treatment response, prostate cancer, pancreatic cancer, malignant progression
- MeSH terms
- Animals, Hypoxia, Humans, Male, Neoplasms, Oxygen, Cell Hypoxia, Disease Progression
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