Cited by 111Cancer, Hypoxia, and MetabolismAngiogenesis and VEGF in CancerHeterocyclic Compound Synthesis and Bioactivity

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HIF-1 Signaling in Drug Resistance to Chemotherapy

Warfel, N.A., El-Deiry, W.S.·2014·Current Medicinal Chemistry

DOI 10.2174/0929867321666140414101056

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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.

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Retracted

Authors: Warfel, N. A., & El-Deiry, W. S.
ORCID: Warfel, N.A.
Venue: Current Medicinal Chemistry
Publisher: Bentham Science Publishers Ltd.
Published: 2014-04-13
Volume: 21
Issue: 26
Pages: 3021-3028
ISSN: 0929-8673 (ISSN-L)
DOI: 10.2174/0929867321666140414101056
OpenAlex: W1982621240
Cited by: 109
References: 0
Citations by year: 2026: 3 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 17 · 2018: 10 · 2017: 11 · 2016: 11 · 2015: 13 · 2014: 3
FWCI: 4.05
Type: journal article
Language: en
Open access: closed
Locations: Current Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Physical Sciences › Chemistry › Organic Chemistry › Heterocyclic Compound Synthesis and Bioactivity
Keywords: HIF-1 signaling, HIF-1, chemoresistance, tumor hypoxia, HIF-1α degradation, HIF-1 inhibitors, epigenetic regulation, apoptosis inhibition, senescence, drug efflux, cellular metabolism, cancer therapy
MeSH terms: Humans, Neoplasms, Signal Transduction, Apoptosis, Drug Resistance, Neoplasm, Hypoxia-Inducible Factor 1, Molecular Targeted Therapy

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HIF-1 Signaling in Drug Resistance to Chemotherapy

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