title: Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery:hypoxia-inducible factor-1 (HIF-1)-active cells as a target for cancer therapy.
abstract: The microenvironment of solid tumors is characterized by low pO(2) that is well below physiological levels. Intratumoral hypoxia is a major factor contributing to cancer progression and is exacerbated as a result of oxygen consumption by rapidly proliferating tumor cells near blood vessels, poor lymphatic drainage resulting in high interstitial pressure, and irregular blood supply through immature tumor vasculature. Hypoxia-inducible factor-1 (HIF-1) is the main transcription factor that regulates cellular responses to hypoxia. Cellular changes induced by HIF-1 are extremely important targets for cancer therapy. Therefore, targeting strategies to counteract HIF-1-active cells are essential for cancer therapy. In this study, we introduce a novel strategy for targeting HIF-1-active cells.
authors.affiliation: Department of Biomolecular Engineering, Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology, Japan. skondoh@bio.titech.ac.jp
authors.forename: Shinae
authors.initials: S
authors.lastname: Kizaka-Kondoh
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuchimaru
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kadonosono
mesh_terms: D000818:Animals; D054697:Cytostatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D057054:Molecular Imaging / Q000379:methods; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000494:pharmacology; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D054697:Cytostatic Agents; D051793:Hypoxia-Inducible Factor 1; D011355:Prodrugs