Hypoxia inducible factor pathway inhibitors as anticancer therapeutics

• Type of Material: Article
• Authors: Sarah K Burroughs, Georgia State University; Stefan Kaluz, Emory University; Danzhu Wang, Georgia State University; Ke Wang, Georgia State University; Erwin Van Meir, Emory University; Binghe Wang, Georgia State University
• Language: English
• Date: 2013-04-01
• Publisher: Future Science: Newlands Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Future Science Ltd.
• Final Published Version (URL): http://dx.doi.org/10.4155/FMC.13.17
• Title of Journal or Parent Work: Future Medicinal Chemistry
• ISSN: 1756-8919
• Volume: 5
• Issue: 5
• Start Page: 553
• End Page: 572
• Grant/Funding Information: EG Van Meir received financial support from the NIH (Grant R01CA116804), the St. Baldrick, the MaxCure, Samuel Waxman Cancer Research and V foundations.
• Keywords: TUMOR-GROWTH; BINDING-SITES; TRANSCRIPTIONAL ACTIVITY; PHASE-II TRIAL; FACTOR 1-ALPHA; FACTOR (HIF)-1-ALPHA; SMALL-MOLECULE INHIBITOR; Life Sciences & Biomedicine; Science & Technology; ONCOLYTIC ADENOVIRUS; CHROMOBACTERIUM-VIOLACEUM NO-968; Pharmacology & Pharmacy; Chemistry, Medicinal; GROWTH-FACTOR GENE
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Hypoxia is a significant feature of solid tumor cancers. Hypoxia leads to a more malignant phenotype that is resistant to chemotherapy and radiation, is more invasive and has greater metastatic potential. Hypoxia activates the hypoxia inducible factor (HIF) pathway, which mediates the biological effects of hypoxia in tissues. The HIF complex acts as a transcription factor for many genes that increase tumor survival and proliferation. To date, many HIF pathway inhibitors indirectly affect HIF but there have been no clinically approved direct HIF inhibitors. This can be attributed to the complexity of the HIF pathway, as well as to the challenges of inhibiting protein-protein interactions.