Antiangiogenic therapy, hypoxia, and metastasis: risky liaisons, or not?
Abstract
All human cells, including cancer cells, need oxygen and nutrients to survive. A widely used strategy to combat cancer is therefore the starvation of tumor cells by cutting off the blood supply of tumors. Clinical experience indeed shows that tumor progression can be delayed by anti-angiogenic agents. However, emerging evidence indicates that in certain experimental conditions, hypoxia as a result of pruning of the tumor microvasculature can promote tumor invasion and metastasis, although these findings are contextual and debated. Genetic studies in mice unveiled that vascular-targeting strategies that avoid aggravation of tumor hypoxia or even promote tumor oxygenation might prevent such an invasive metastatic switch. In this article, we will discuss the emerging link between hypoxia signaling and the various steps of metastasis.
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Hypoxia and activation of HIF signaling influence multiple steps within the metastatic cascade, including invasion and migration, intravasation and extravasation, establishment of the premetastatic niche, and survival and growth at the distant site.
“Hypoxia and activation of HIF signaling influence multiple steps within the metastatic cascade, including invasion and migration, intravasation and extravasation, and establishment of the premetastatic niche, as well as survival and growth at the distant site”
From Hypoxic control of metastasis (2016) · cites this paper as [48]
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- Authors
- De Bock, K., Mazzone, M., & Carmeliet, P.
- Affiliations
- KU Leuven (BE)
- Corresponding author
- Carmeliet, Peter
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2011-05-31
- Volume
- 8
- Issue
- 7
- Pages
- 393-404
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W1989402742
- Cited by
- 293
- References
- 149
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 13 · 2023: 17 · 2022: 19 · 2021: 24 · 2020: 20 · 2019: 12 · 2018: 17 · 2017: 15 · 2016: 20 · 2015: 31 · 2014: 30 · 2013: 31 · 2012: 27
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- anti-angiogenic therapy, tumor hypoxia, metastasis, tumor invasion, hypoxia signaling, tumor microvasculature, tumor oxygenation, vascular targeting agents, tumor starvation
- MeSH terms
- Animals, Hypoxia, Humans, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Angiogenesis Inhibitors, Mice
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.
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