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HIF-1 Signaling in Drug Resistance to Chemotherapy
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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In the citing paper
“Numerous reports demonstrated that inhibition of HIF-1α could overcome resistance of tumor cells to chemotherapy [25, 26].”
From Inhibition of HIF-1α by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma (2015) · cites this paper as [25]
In the citing paper
“HIF-1α is an important transcription factor for tumor growth, invasion, angiogenesis, metabolism and drug resistance [7, 10, 25].”
From Inhibition of HIF-1α by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma (2015) · cites this paper as [25]
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Cited by
Unveiling the mechanisms and challenges of cancer drug resistance
Khan, S. U., Fatima, K., Aisha, S., & Malik, F. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01302-1 · Cited by 417
Collagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance
Xiong, G., Stewart, R. L., Chen, J., Gao, T., Scott, T. L., Samayoa, L. M., O’Connor, K. L., Lane, A. N., & Xu, R. (2018) · Nature Communications · doi:10.1038/s41467-018-06893-9 · Cited by 285
Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment
Wu, P., Gao, W. Q., Su, M., Nice, E. C., Zhang, W., Lin, J., & Xie, N. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.641469 · Cited by 226
PIM kinase (and Akt) biology and signaling in tumors
Warfel, N. A., & Kraft, A. S. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.03.001 · Cited by 210
Self-citationDevelopment of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy
Yu, T., Tang, B., & Sun, X. (2017) · Yonsei Medical Journal · doi:10.3349/ymj.2017.58.3.489 · Cited by 202
Metadata
- 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)
- 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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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
