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The molecular basis of the hypoxia response pathway: Tumour hypoxia as a therapy target

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Abstract

Hypoxia induces a cascade of physiological responses that includes glycolysis, erythropoiesis, angiogenesis, changes in adrenergic signal transduction and vascular cellular proliferation. Hypoxia-inducible genes are relevant to growth and behaviour of cancer as well as the adaptation and survival of normal tissues. Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric DNA binding complex composed of two basic-helix-loop-helix PAS-proteins: HIF-1 beta/ARNT (aryl hydrocarbon receptor nuclear translocator), which is constitutively expressed, and HIF-1 alpha, which is not present in normoxic cells but induced under hypoxic conditions. Recently another member of the bHLH-PAS family, EPAS-1 has been reported and shares similar properties with HIF-1 alpha, although it is considered endothelial specific. In addition, the presence of other DNA-binding motifs in the promoter of hypoxia-inducible genes highlight the occurrence of cross-talk between transcription factors in the modulation of hypoxic gene expression. In this review, we present a survey of the hypoxia response pathway and we discuss attempts to use gene therapy activated by the low oxygen environment or by necrotic regions of tumours.

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Authors and Affiliations

  1. Imperial Cancer Research Fund, Molecular Oncology Laboratory, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

    Christine Blancher & Adrian L. Harris

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  1. Christine Blancher
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  2. Adrian L. Harris
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Blancher, C., Harris, A.L. The molecular basis of the hypoxia response pathway: Tumour hypoxia as a therapy target. Cancer Metastasis Rev 17, 187–194 (1998). https://doi.org/10.1023/A:1006002419244

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