title: Ionizing radiation: a genetic switch for cancer therapy.
abstract: Gene therapy of cancer represents a promising but challenging area of therapeutic research. The discovery of radiation-inducible genes led to the concept and development of radiation-targeted gene therapy. In this approach, promoters of radiation-inducible genes are used to drive transcription of transgenes in the response to radiation. Constructs in which the radiation-inducible promoter elements activate a transgene encoding a cytotoxic protein are delivered to tumors by adenoviral vectors. The tumoricidal effects are then localized temporally and spatially by X-rays. We review the conceptual development of TNFerade, an adenoviral vector containing radiation-inducible elements of the early growth response-1 promoter upstream of a cDNA encoding human tumor necrosis factor-alpha. We also summarize the preclinical work and clinical trials utilizing this vector as a treatment for diverse solid tumors.
authors.affiliation: Department of Surgery, The University of Chicago Hospitals, IL 60637, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Mezhir
authors.forename: K D
authors.initials: KD
authors.lastname: Smith
authors.forename: M C
authors.initials: MC
authors.lastname: Posner
authors.forename: N
authors.initials: N
authors.lastname: Senzer
authors.forename: B
authors.initials: B
authors.lastname: Yamini
authors.forename: D W
authors.initials: DW
authors.lastname: Kufe
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy*; D011401:Promoter Regions, Genetic; D011839:Radiation, Ionizing; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000528:radiation effects / Q000627:therapeutic use
chemical_list: D051766:Early Growth Response Protein 1; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha