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 "nonselective" HIF-1 inhibitors have been identified, which are either in the clinic or under development. In this article, we discuss how topoisomerase I poisons, which inhibit HIF-1a protein accumulation and transcriptional activity, can be "rationally" used to target HIF-1 for cancer therapy.
MeSH terms
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Antineoplastic Agents / pharmacology
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Cell Hypoxia / physiology
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Cyclooxygenase 2
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DNA Topoisomerases, Type I / metabolism*
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / physiology
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Helix-Loop-Helix Motifs / physiology
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Humans
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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Isoenzymes / metabolism
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Membrane Proteins
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / metabolism*
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Prostaglandin-Endoperoxide Synthases / metabolism
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Signal Transduction / physiology
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Topoisomerase I Inhibitors
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Topotecan / pharmacology*
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Transcription Factors*
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Tumor Cells, Cultured
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Antineoplastic Agents
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DNA-Binding Proteins
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HIF1A protein, human
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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Isoenzymes
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Membrane Proteins
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Nuclear Proteins
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Topoisomerase I Inhibitors
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Transcription Factors
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Vascular Endothelial Growth Factor A
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Topotecan
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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DNA Topoisomerases, Type I