The DOI matches its Crossref record.
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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Li, R., Sui, B., Leng, D., He, S., Liu, K., & Bo, X. (2024) · Advanced Intelligent Systems · doi:10.1002/aisy.202400180 · Cited by 1
A PlGF-1 Derived Peptide Inhibits Angiogenesis via HIF-1β/VEGF Pathway
Wang, W., Gu, Q., Xu, X., & Zheng, Y. (2016) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-016-9567-z
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Mahn, F., Franck, S., Czauderna, C., & Marquardt, J. U. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788016506-00294
Ma, H. L. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.75.2022.tde-22062022-114254
Yi, H. L. (2025) · International Journal of Clinical and Experimental Pathology · doi:10.62347/qvon7675
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Ramakrishnan, S. K. (2019) · The Conversation · doi:10.64628/aai.dfvrkksgw
Heterogenicity of cancer and drug resistance
Gupta, U., Mishra, S., Sharma, M., & Bhardwaj, N. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44185-1.00019-7
HIF-1 signaling contributes to lenvatinib resistance in patient-derived HCC organoids
Huang, Y., Ai, Z., & Huang, S. (2026) · Genomics · doi:10.1016/j.ygeno.2026.111310
Xue, W. Y., Wang, Y. Z., Chuprov‐Netochin, R. N., Pustovalova, M. V., Kuzmin, D. V., & Leonov, S. V. (2026) · Molecular Biology · doi:10.1134/s0026893326700184
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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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Data sources
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.
