Targeting topoisomerase I to inhibit hypoxia inducible factor 1.
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.
Rapisarda
Annamaria
A
Developmental Therapeutics Program, Science Applications International Corporation, Frederick, Inc; National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
Shoemaker
Robert H
RH
Melillo
Giovanni
G
D000970:Antineoplastic Agents / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology; D051546:Cyclooxygenase 2; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D018257:Helix-Loop-Helix Motifs / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000494:pharmacology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D008565:Membrane Proteins; D009687:Nuclear Proteins; D059004:Topoisomerase I Inhibitors; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D019772:Topotecan; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D004264:DNA Topoisomerases, Type I