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The impact of O2 availability on human cancer

Nature Reviews Cancer volume 8, pages 967–975 (2008)Cite this article

Abstract

During the past century it has been established that regions within solid tumours experience mild to severe O2 deprivation owing to aberrant vascular function. These hypoxic regions are associated with altered cellular metabolism, as well as increased resistance to radiation and chemotherapy. As discussed in this Timeline, over the past decade work from many laboratories has elucidated the mechanisms by which hypoxia-inducible factors (HIFs) modulate tumour cell metabolism, angiogenesis, growth and metastasis. The central role played by intra-tumoural hypoxia and HIF in these processes has made them attractive therapeutic targets in the treatment of multiple human malignancies.

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Figure 1: Genes activated by hypoxia-inducible factors (HIFs) that are involved in tumour progression.
Figure 2: Regulation of hypoxia-inducible factor-α (HIFα) subunits by O2 availability and other intracellular metabolites.
Figure 3: Hypoxia regulates other crucial pathways that affect tumour progression in a HIF-independent fashion.

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Acknowledgements

We would like to thank all members of the Simon laboratory for helpful comments as well as F. Tucker and E. Podewils for manuscript preparation.

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  1. Jessica A. Bertout, Shetal A. Patel and M. Celeste Simon are at the Abramson Family Cancer Research Institute, Jessica A. Bertout is also at the School of Veterinary Medicine, Shetal A. Patel, and M. Celeste Simon are at the School of Medicine, and M. Celeste Simon is at the Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.,

    Jessica A. Bertout, Shetal A. Patel & M. Celeste Simon

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  1. Jessica A. Bertout
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DATABASES

National Cancer Institute Drug Dictionary 

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Cu-ATSM

etanidazole

everolimus

FDG

gefitinib

misonidazole

sorafenib

tirapazamine

Pathway Interaction Database

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Bertout, J., Patel, S. & Simon, M. The impact of O2 availability on human cancer. Nat Rev Cancer 8, 967–975 (2008). https://doi.org/10.1038/nrc2540

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