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The Complexity of the HIF-1-Dependent Hypoxic Response in Breast Cancer Presents Multiple Avenues for Therapeutic Intervention

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Pharmaceutical Perspectives of Cancer Therapeutics

Abstract

A critical aspect of tumor physiology is the sensation of oxygen in the microenvironment. The oxygen-responsive Hypoxia-Inducible Factor (HIF)-1α protein is a master transcriptional regulator of the hypoxic response, controlling expression of a variety of genes related to metabolism, glucose transport, cell cycle progression, cell migration, multidrug resistance, and angiogenesis. Several studies have demonstrated that over-expression HIF-1α protein in breast cancer correlates with poor prognosis, increased risk of metastasis and decreased survival. Moreover, hypoxic regions of tumors are believed to be the source of tumor cells that are resistant to radiation and chemotherapy. More recently, it has also been proposed that hypoxia stimulates expansion of normal and cancer stem cells. Despite a complete understanding of how HIF-1α impacts breast cancer progression and metastasis, the HIF-1α pathway is ideal for targeting drug design since interfering with a master regulator of the hypoxic response could disrupt multiple downstream processes essential to tumor cell self-renewal, expansion, dissemination, and metastatic colonization.

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  1. Center for Cancer Research, Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA

    Tiffany N. Seagroves

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    Seagroves, T.N. (2009). The Complexity of the HIF-1-Dependent Hypoxic Response in Breast Cancer Presents Multiple Avenues for Therapeutic Intervention. In: Lu, Y., Mahato, R. (eds) Pharmaceutical Perspectives of Cancer Therapeutics. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0131-6_16

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