Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies
Abstract
Tissue hypoxia occurs where there is an imbalance between oxygen supply and consumption. Hypoxia occurs in solid tumours as a result of an inadequate supply of oxygen, due to exponential cellular proliferation and an inefficient vascular supply. It is an adverse prognostic indicator in cancer as it is associated with tumour progression and resistance to therapy. The expression of several genes controlling tumour cell survival are regulated by hypoxia, e.g., growth factors governing the formation of new blood vessels, and hypoxia-responsive transcription factors modulating the expression of genes, which promote tumour cell survival. This review outlines some of the pathways by which tumour hypoxia leads to chemotherapeutic resistance, directly due to lack of oxygen availability, and indirectly due to alterations in the proteome/genome, angiogenesis and pH changes. Some innovative therapies are also detailed which may potentially minimise or eliminate these problems associated with targeting solid tumours.
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Hypoxia is a major driver of multiple drug resistance (MDR) to chemotherapeutic drugs.
“Hypoxia is considered to be a major driver of multiple drug resistance (MDR) to chemotherapeutic drugs. 378 , 379”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [378]
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Flagged first, then by citations
Cited by
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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 · see citing works
Hypoxia, DNA repair and genetic instability
Bristow, R. G., & Hill, R. P. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2344 · Cited by 1,140 · see citing works
3D cell culture systems modeling tumor growth determinants in cancer target discovery
Thoma, C. R., Zimmermann, M., Agarkova, I., Kelm, J. M., & Krek, W. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.03.001 · Cited by 478 · see citing works
A Review of Three-Dimensional In Vitro Tissue Models for Drug Discovery and Transport Studies
Elliott, N. T., & Yuan, F. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22257 · Cited by 449 · see citing works
Macrophage Responses to Hypoxia
Lewis, C., & Murdoch, C. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62038-x · Cited by 413 · see citing works
Däster, S., Amatruda, N., Calabrese, D., Ivanek, R., Turrini, E., Droeser, R. A., Zajac, P., Fimognari, C., Spagnoli, G. C., Iezzi, G., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.13857 · Cited by 281 · see citing works
Modulating tumor hypoxia by nanomedicine for effective cancer therapy
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Chawla, S. P., Cranmer, L. D., Van Tine, B. A., Reed, D. R., Okuno, S. H., Butrynski, J. E., Adkins, D. R., Hendifar, A. E., Kroll, S., & Ganjoo, K. N. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.54.3660 · Cited by 155 · see citing works
Li, F., Mei, H., Gao, Y., Xie, X., Nie, H., Li, T., Zhang, H., & Jia, L. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.08.030 · Cited by 152 · see citing works
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Hypoxia signaling in cancer: Implications for therapeutic interventions
Zhuang, Y., Liu, K., He, Q., Gu, X., Jiang, C., & Wu, J. (2023) · MedComm · doi:10.1002/mco2.203 · Cited by 119 · see citing works
Progress toward Overcoming Hypoxia-Induced Resistance to Solid Tumor Therapy
Reginato, M., & Karakashev, S. (2015) · Cancer Management and Research · doi:10.2147/cmar.s58285 · Cited by 95 · see citing works
Schietroma, M., Cecilia, E. M., Carlei, F., Sista, F., De Santis, G., Piccione, F., & Amicucci, G. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-012-2714-7 · Cited by 92 · see citing works
Metal peroxides for cancer treatment
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RetractedNormobaric hyperoxia inhibits the progression of lung cancer by inducing apoptosis
Kim, S. W., Kim, I. K., Ha, J. H., Yeo, C. D., Kang, H. H., Kim, J. W., & Lee, S. H. (2018) · Experimental Biology and Medicine · doi:10.1177/1535370218774737 · Cited by 25 · see citing works
- Authors
- Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M., & Toomey, D.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Corresponding author
- Toomey, Deirdre
- ORCID
- Condron, Claire M
- Venue
- Cancer Treatment Reviews
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 29
- Issue
- 4
- Pages
- 297-307
- ISSN
- 0305-7372 (ISSN-L)
- OpenAlex
- W2112645200
- Cited by
- 559
- References
- 119
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 27 · 2023: 27 · 2022: 24 · 2021: 38 · 2020: 29 · 2019: 30 · 2018: 33 · 2017: 28 · 2016: 30 · 2015: 31 · 2014: 41 · 2013: 27 · 2012: 26
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Treatment Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- tumor hypoxia, chemoresistance, solid tumors, angiogenesis, tumor cell survival, tumor microenvironment, tumor pH, hypoxia-targeted therapy, prognostic factors
- MeSH terms
- Tirapazamine, Acidosis, Respiratory, Animals, Antineoplastic Agents, DNA-Binding Proteins, Humans, Hydrogen-Ion Concentration, Lymphokines, Macrophages, Mutation, Neoplasms, Neovascularization, Pathologic, Nuclear Proteins, Oxygen Consumption, Risk Factors, Transcription Factors, Triazines, Genetic Therapy, Cell Hypoxia, Tumor Suppressor Protein p53, Endothelial Growth Factors, Apoptosis, Drug Resistance, Neoplasm, Intercellular Signaling Peptides and Proteins, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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