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Hypoxia-Directed Drug Strategies to Target the Tumor Microenvironment

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Tumor Microenvironment and Cellular Stress

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

Abstract

Hypoxia is an important component of the tumor microenvironment and has been the target of drug discovery efforts for almost half a century. These efforts have evolved from offsetting the impact of hypoxia on radiotherapy with oxygen-mimetic radiosensitizers to using hypoxia as a means to selectively target tumors. The more recent description of hypoxia-inducible factors and their role in the hypoxia response network has revealed a host of new drug targets to selectively target tumors. We are developing hypoxia-directed drugs in each of the following areas: novel radiosensitizers for hypofractionated radiotherapy, a second-generation benzotriazine di-N-oxide hypoxia-activated prodrug, and a hypoxia-inducible factor-1–dependent cytotoxin that targets glucose transport. These projects are discussed in the context of hypoxia-directed drug discovery.

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Authors and Affiliations

  1. Auckland Cancer Society Research Centre, The University of Auckland, 92019, Auckland, 1142, New Zealand

    Michael P. Hay Ph.D., Kevin O. Hicks Ph.D. & Jingli Wang Ph.D.

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  1. Michael P. Hay Ph.D.
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  2. Kevin O. Hicks Ph.D.
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  3. Jingli Wang Ph.D.
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Correspondence to Michael P. Hay Ph.D. .

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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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Hay, M.P., Hicks, K.O., Wang, J. (2014). Hypoxia-Directed Drug Strategies to Target the Tumor Microenvironment. 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_6

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