The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Tumor Hypoxia as a Barrier in Cancer Therapy: Why Levels Matter
Open accessAbstract
Hypoxia arises in tumor regions with insufficient oxygen supply and is a major barrier in cancer treatment. The distribution of hypoxia levels is highly heterogeneous, ranging from mild, almost non-hypoxic, to severe and anoxic levels. The individual hypoxia levels induce a variety of biological responses that impair the treatment effect. A stronger focus on hypoxia levels rather than the absence or presence of hypoxia in our investigations will help development of improved strategies to treat patients with hypoxic tumors. Current knowledge on how hypoxia levels are sensed by cancer cells and mediate cellular responses that promote treatment resistance is comprehensive. Recently, it has become evident that hypoxia also has an important, more unexplored role in the interaction between cancer cells, stroma and immune cells, influencing the composition and structure of the tumor microenvironment. Establishment of how such processes depend on the hypoxia level requires more advanced tumor models and methodology. In this review, we describe promising model systems and tools for investigations of hypoxia levels in tumors. We further present current knowledge and emerging research on cellular responses to individual levels, and discuss their impact in novel therapeutic approaches to overcome the hypoxia barrier.
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1 retracted
Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., & Semenza, G. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800102200 · Cited by 1,601
RetractedTumor Hypoxia: Definitions and Current Clinical, Biologic, and Molecular Aspects
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Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
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Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
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Microenvironmental regulation of tumour angiogenesis
De Palma, M., Biziato, D., & Petrova, T. V. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.51 · Cited by 1,847
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Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells
Facciabene, A., Peng, X., Hagemann, I. S., Balint, K., Barchetti, A., Wang, L.-P., Gimotty, P. A., Gilks, C. B., Lal, P., Zhang, L., et al. (2011) · Nature · doi:10.1038/nature10169 · Cited by 1,376
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Cited by
Stimuli-Responsive Polymer-Based Nanosystems for Cancer Theranostics
Wei, D., Sun, Y., Zhu, H., & Fu, Q. (2023) · ACS Nano · doi:10.1021/acsnano.3c06019 · Cited by 303
Bai, R., Li, Y., Jian, L., Yang, Y., Zhao, L., & Wei, M. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01645-2 · Cited by 279
Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 83
“These central regions are poorly perfused and metabolically stressed, whereas peripheral tumor cells—being in closer proximity to functional vasculature—exhibit higher proliferative indices [106].”
Zhu, J., Yan, J., Zhang, Y., Zhu, X., & Chen, G. (2026) · Mammalian Genome · doi:10.1007/s00335-026-10202-x · Cited by 3
Metadata
- Authors
- Hompland, T., Fjeldbo, C. S., & Lyng, H.
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2021-01-28
- Volume
- 13
- Issue
- 3
- Pages
- 499
- ISSN
- 2072-6694 (ISSN-L)
- OpenAlex
- W3122483411
- Cited by
- 179
- References
- 36
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- gold
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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