title: Hypoxia-directed drug strategies to target the tumor microenvironment.
abstract: Hypoxia is an important component of the tumor microenvironment and has been the target of drug discovery efforts for almost half a century. These efforts have evolved from offsetting the impact of hypoxia on radiotherapy with oxygen-mimetic radiosensitizers to using hypoxia as a means to selectively target tumors. The more recent description of hypoxia-inducible factors and their role in the hypoxia response network has revealed a host of new drug targets to selectively target tumors. We are developing hypoxia-directed drugs in each of the following areas: novel radiosensitizers for hypofractionated radiotherapy, a second-generation benzotriazine di-N-oxide hypoxia-activated prodrug, and a hypoxia-inducible factor-1-dependent cytotoxin that targets glucose transport. These projects are discussed in the context of hypoxia-directed drug discovery.
authors.affiliation: Auckland Cancer Society Research Centre, The University of Auckland, 92019, Auckland, 1142, New Zealand, m.hay@auckland.ac.nz.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hay
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Hicks
authors.forename: Jingli
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000235:genetics; D004260:DNA Repair / Q000502:physiology; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D051793:Hypoxia-Inducible Factor 1; D011838:Radiation-Sensitizing Agents