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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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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