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Angiogenesis Inhibition pp 15–34Cite as

HIF-1α and Cancer Therapy

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Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 180))

Abstract

Most solid tumors develop regions of hypoxia as they grow and outstrip their blood supply. In order to survive in the stressful hypoxic environment, tumor cells have developed a coordinated set of responses orchestrating their adaptation to hypoxia. The outcomes of the cellular responses to hypoxia are aggressive disease, resistance to therapy, and decreased patient survival. A critical mediator of the hypoxic response is the transcription factor hypoxia-inducible factor 1 (HIF-1) that upregulates expression of proteins that promote angiogenesis, anaerobic metabolism, and many other survival pathways. Regulation of HIF-1α, a component of the HIF-1 heterodimer, occurs at multiple levels including translation, degradation, and transcriptional activation, and serves as a testimony to the central role of HIF-1. Studies demonstrating the importance of HIF-1α expression for tumor survival have made HIF-1α an attractive target for cancer therapy. The growing l.ist of pharmacological inhibitors of HIF-1 and their varied targets mirrors the complex molecular mechanisms controlling HIF-1. In this chapter, we summarize recent findings regarding the regulation of HIF-1α and the progress made in identifying new therapeutic agents that inhibit HIF-1α.

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Aknowledgments Supported by NIH grants CA0179094, CA095060, CA0179094 and CA109552.

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  1. MD Anderson Cancer Center, 1400 Holcombe Blvd., FC6.3044, Unit 422, Houston, TX, 77030, USA

    Garth Powis

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  1. Mei Yee Koh
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  2. Taly R. Spivak-Kroizman
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  3. Garth Powis
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  1. Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, Münster, 48149, Germany

    Rüdiger Liersch

  2. Medizinische Klinik und Poliklinik, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, Münster, 48149, Germany

    Wolfgang E. Berdel

  3. Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, Münster, 48149, Germany

    Torsten Kessler

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Koh, M.Y., Spivak-Kroizman, T.R., Powis, G. (2010). HIF-1α and Cancer Therapy. In: Liersch, R., Berdel, W., Kessler, T. (eds) Angiogenesis Inhibition. Recent Results in Cancer Research, vol 180. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78281-0_3

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