Ionizing radiation: a genetic switch for cancer therapy.
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.
Mezhir
J J
JJ
Department of Surgery, The University of Chicago Hospitals, IL 60637, USA.
Smith
K D
KD
Posner
M C
MC
Senzer
N
N
Yamini
B
B
Kufe
D W
DW
Weichselbaum
R R
RR
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
D051766:Early Growth Response Protein 1; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha