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Implications of Oxygen Homeostasis for Tumor Biology and Treatment

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Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 903))

Abstract

Tumors serve as a prototype system to study the role of the hypoxic microenvironment and gain insight in the regulation oxygen homeostasis. A series of biochemical and cell biological studies have significantly extended our knowledge of how tumor cells activate key regulatory mechanisms of oxygen homeostasis not only to adapt to the hostile tumor microenvironment but also to acquire a more aggressive tumor phenotype. Reduced oxygen levels and tumor-specific genetic alterations synergistically drive tumor progression by activating a key transcriptional system, the hypoxia inducible factors (HIFs). HIFs trigger a set of adaptive responses commonly associated with tumor malignancy including tumor angiogenesis, a shift in metabolism, proliferation, invasion, and metastasis. We and others could demonstrate that cancer stem cells are controlled by HIFs within a hypoxic niche, establishing an intriguing link between the well known function of hypoxia in tumor growth and stem cell biology. Additionally, HIF activation potentially conveys resistance to current tumor therapies including the evasive resistance phenotype observed after anti-angiogenic treatment. Together, these findings provide strong evidence that activation of the HIF system is a decisive step in cancer progression that critically shapes therapy response and clinical outcome. Recent insight into the precise mechanisms of oxygen sensing and signalling has offered new promising and potentially selective strategies to counteract this crucial pathway.

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Acknowledgements

This work was supported by grants from the DFG (KFO210, AC 110/4-1; EXC 147/1), LOEWE (OSF), the Deutsche Krebshilfe (111719), the von Behring-Röntgen Foundation (58-0069; 59-0037), the RKA-Förderpool and the UKGM Kooperationsvertrag.

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  1. Institute of Neuropathology, Justus Liebig University, Giessen, 35392, Germany

    Boyan K. Garvalov & Till Acker

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  1. Boyan K. Garvalov
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  2. Till Acker
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Correspondence to Till Acker .

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  1. Altitude Research Center, University of Colorado Anschutz Medical, AURORA, Colorado, USA

    Robert C. Roach

  2. Institute for Altitude Medicine, Telluride, Colorado, USA

    Peter H. Hackett

  3. Division of Physiology 0623A, University of California - San Diego, La Jolla, California, USA

    Peter D. Wagner

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Garvalov, B.K., Acker, T. (2016). Implications of Oxygen Homeostasis for Tumor Biology and Treatment. In: Roach, R., Hackett, P., Wagner, P. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 903. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7678-9_12

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