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Hypoxia and Metabolism in Cancer

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Tumor Microenvironment and Cellular Stress

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 772))

Abstract

Interest in targeting metabolism has been renewed in recent years as research increases understanding of the altered metabolic profile of tumor cells compared with that of normal cells. Metabolic reprogramming allows cancer cells to survive and proliferate in the hostile tumor microenvironment. These metabolic changes support energy generation, anabolic processes, and the maintenance of redox potential, mechanisms that are all essential for the proliferation and survival of tumor cells. The metabolic switch in a number of key metabolic pathways is mainly regulated by genetic events, rendering cancer cells addicted to certain nutrients, such as glutamine. In addition, hypoxia is induced when highly proliferative tumor cells distance themselves from an oxygen supply. Hypoxia-inducible factor 1α is largely responsible for alterations in metabolism that support the survival of hypoxic tumor cells. Metabolic alterations and dependencies of cancer cells may be exploited to improve anticancer therapy. This chapter reviews the main aspects of altered metabolism in cancer cells, emphasizing recent advances in glucose, glutamine, and lipid metabolism.

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Acknowledgments

The authors thank E. Favaro and A. McIntyre for their critical reading and feedback. K.B. is supported by a Cancer Research UK fellowship. A.L.H. is funded by Cancer Research UK, the Oxford Cancer Imaging Centre, the Breast Cancer Research Foundation, and the Oxford NIHR Biomedical Research Centre.

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Authors and Affiliations

  1. CRUK Hypoxia and Angiogenesis Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DS, UK

    Karim Bensaad

  2. CRUK Growth Factor Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DS, UK

    Adrian L. Harris

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  1. Karim Bensaad
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Correspondence to Karim Bensaad .

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  1. Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

    Constantinos Koumenis

  2. Cancer Research, Gray Institute for Radiation Oncology, Oxford, United Kingdom

    Ester Hammond

  3. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA

    Amato Giaccia

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Bensaad, K., Harris, A.L. (2014). Hypoxia and Metabolism in Cancer. In: Koumenis, C., Hammond, E., Giaccia, A. (eds) Tumor Microenvironment and Cellular Stress. Advances in Experimental Medicine and Biology, vol 772. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5915-6_1

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