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Cited by 41Cancer, Hypoxia, and MetabolismCancer therapeutics and mechanismsBioactive Compounds and Antitumor Agents

Targeting Topoisomerase 1 to inhibit Hypoxia Inducible Factor 1

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Rapisarda, Annamaria, Shoemaker, Robert H., Melillo, Giovanni·2004·Cell Cycle
DOI 10.4161/cc.3.2.688
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Abstract

HIF-1 is a key factor in cancer progression. Efforts are underway to identify and develop small molecules that inhibit HIF-1 transcriptional activity. What are the best targets and the best ways to develop HIF-1 inhibitors are open questions. However, several “non-selective” HIF-1 inhibitors have been identified, which are either in the clinic or under development. In this article, we discuss how topoisomerase 1 poisons, which inhibit HIF-1a protein accumulation and transcriptional activity, can be “rationally” used to target HIF-1 for cancer therapy.

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  • Topoisomerase inhibitors have emerged as unexpected, noncanonical modulators of HIF activity.

    “Topoisomerase inhibitors have emerged as unexpected, noncanonical modulators of HIF activity [299], opening an attractive, though mechanistically challenging - avenue for drug repurposing aimed at suppressing hypoxia-driven transcription.”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [299]

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Cited by 41

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Authors
Rapisarda, A., Shoemaker, R. H., & Melillo, G.
Affiliations
  • Leidos (United States) (US)
  • Frederick National Laboratory for Cancer Research (US)
ORCID
Shoemaker, Robert H.
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2004-02
Volume
3
Issue
2
Pages
167-170
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.4161/cc.3.2.688
OpenAlex
W4322701573
Cited by
41
References
0
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 1
FWCI
1.79
Type
journal article
Language
en
Open access
Locations
Cell Cycle (publishedVersion)
Funders
  • National Institutes of Health (N01-CO-12400)
  • National Cancer Institute (CO-12400, N01CO12400)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Keywords
topoisomerase I inhibitor, HIF-1, HIF-1 inhibition, HIF-1 transcriptional activity, cancer therapy, small molecule inhibitors, rational drug design

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