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Hypoxia and Hypoxia Inducible Factors (HIF) as Important Regulators of Tumor Physiology

  • Chapter
Angiogenesis in Brain Tumors

Part of the book series: Cancer Treatment and Research ((CTAR,volume 117))

Abstract

Regions of low oxygen tension are common findings in malignant tumors and are associated with increased frequency of tumor invasion and metastasis. Indeed, the ability to initiate homeostatic responses and adapt to hypoxia, e.g. by induction of angiogenesis, represents an important and crucial aspect in solid tumor growth. A significant advance in our understanding of the hypoxia response stems from the discovery of the hypoxia inducible factors (HIF) which act as key regulators of hypoxia-induced gene expression. Both, low levels of oxygen, apparently via reduced activity of a recently identified class of 2oxoglutarate dependent oxygenases, and various tumor specific genetic alterations synergistically act to induce the HIF system. A widespread HIF activation can be observed in a variety of malignant tumors including brain tumors. The HIF system induces adaptive responses including angiogenesis, glycolysis, and pH regulation which confer increased resistance towards the hostile tumor microenvironment. Apart from protumorigenic the wide-ranging HIF pathway is known to harbor antitumorigenic components, which may, however, be disabled by tumor specific genetic alterations. Thus, mounting evidence has identified HIF as a crucial regulator of tumor growth and progression constituting an intriguing and novel target for therapeutic intervention.

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Authors and Affiliations

  1. Edinger Institute, Neuropathology, Johann-Wolfgang Goethe University, Deutschordenstr, 46, 60528, Frankfurt, Germany

    Till Acker & Karl H. Plate

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  1. Till Acker
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  2. Karl H. Plate
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Editors and Affiliations

  1. Neurosurgery Carl Gustav Carus Hospital, Technical University of Dresden, Dresden, Germany

    Matthias Kirsch

  2. Neurosurgery Children’s Hospital Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Peter McL. Black

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© 2004 Springer Science+Business Media New York

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Acker, T., Plate, K.H. (2004). Hypoxia and Hypoxia Inducible Factors (HIF) as Important Regulators of Tumor Physiology. In: Kirsch, M., Black, P.M. (eds) Angiogenesis in Brain Tumors. Cancer Treatment and Research, vol 117. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8871-3_14

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  • DOI: https://doi.org/10.1007/978-1-4419-8871-3_14

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  • Print ISBN: 978-1-4613-4699-9

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