HIF-1 Signaling in Drug Resistance to Chemotherapy

ISSN: 1875-533X (Online)
ISSN: 0929-8673 (Print)


Volume 21, 38 Issues, 2014


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HIF-1 Signaling in Drug Resistance to Chemotherapy

Author(s): N.A. Warfel and W.S. El-Deiry

Affiliation: 500 University Drive, Room T4423, Hershey, PA 17033, USA.

Abstract

Activation of hypoxia-inducible factor 1 (HIF-1) signaling is observed in a broad range of human cancers due to tumor hypoxia and epigenetic mechanisms. HIF-1 activation leads to the transcription of a plethora of target genes that promote physiological changes associated with therapeutic resistance, including the inhibition of apoptosis and senescence and the activation of drug efflux and cellular metabolism. As a result, targeting HIF-1 represents an attractive strategy to enhance the efficacy of current therapies as well as reduce resistance to chemotherapy in tumors. Approaches to inhibit HIF-1 signaling have primarily focused on reducing HIF-1α protein levels, by inducing its degradation or inhibiting its transcription, inhibiting HIF-1-mediated transcription, or disrupting the formation of the HIF-1 transcription factor complex. To date, multiple preclinical and clinical agents have been identified that effectively inhibit HIF-1 activity through various mechanisms, likely accounting for a portion of their anti-tumor efficacy. This review aims to provide an overview of our current understanding of the role of HIF-1 in therapeutic resistance and discuss the ongoing effort to develop HIF-1 inhibitors as an anti-cancer strategy.

Keywords: HIF-1, hypoxia-inducible factor-1, hypoxia, therapeutic resistance.

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Article Details

Volume: 21
Issue Number: 26
First Page: 3021
Last Page: 3028
Page Count: 8
DOI: 10.2174/0929867321666140414101056
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