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Review
. 2025 Apr 25;87(6):3635-3659.
doi: 10.1097/MS9.0000000000003334. eCollection 2025 Jun.

Oxygen deprivation in breast cancer: mechanisms, pathways, and implications

Emmanuel Ifeanyi Obeagu  1
Affiliations
Review

Oxygen deprivation in breast cancer: mechanisms, pathways, and implications

Emmanuel Ifeanyi Obeagu. Ann Med Surg (Lond). .

Abstract

Hypoxia, a state of reduced oxygen availability, is a defining feature of the tumor microenvironment in breast cancer. It arises from the rapid proliferation of cancer cells, which outpaces the development of adequate vasculature. This oxygen deprivation triggers a cascade of molecular and cellular adaptations that enable tumor cells to survive and thrive under hostile conditions. Key among these is the stabilization of hypoxia-inducible factors, which regulate genes involved in angiogenesis, metabolic reprogramming, immune evasion, and cell survival. Hypoxia significantly influences breast cancer behavior, promoting tumor aggressiveness, therapeutic resistance, and metastatic potential. The hypoxic microenvironment fosters angiogenesis through vascular endothelial growth factor signaling, albeit leading to abnormal and inefficient vasculature. It also reprograms cancer cell metabolism towards glycolysis, supporting survival and growth in oxygen-deprived regions. Furthermore, hypoxia modulates immune responses, suppressing anti-tumor immunity while promoting the recruitment of immunosuppressive cells. These multifaceted effects underscore hypoxia's pivotal role in shaping the clinical trajectory of breast cancer.

Keywords: breast cancer; hypoxia; hypoxia-inducible factors; therapeutic resistance; tumor microenvironment.

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Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. The author declares no conflict of interest.

Figures

Figure 1.
Figure 1.
Hypoxia-induced adaptations in breast cancer.
Figure 2.
Figure 2.
Hypoxia-induced signaling in breast cancer.
Figure 3.
Figure 3.
Implications of hypoxia in breast cancer.
Figure 4.
Figure 4.
Therapeutic strategies targeting hypoxia in breast cancer.
See this image and copyright information in PMC

References

    1. Bray F, Ferlay J, Soerjomataram I, et al. . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424. - PubMed
    1. Harris AL. Hypoxia – a key regulatory factor in tumour growth. Nat Rev Cancer 2002;2:38–47. - PubMed
    1. Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell 2012;148:399–408. - PMC - PubMed
    1. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011;473:298–307. - PMC - PubMed
    1. Warburg O. On the origin of cancer cells. Science 1956;123:309–14. - PubMed

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