title: Evidence that replication of the antitumor adenovirus ONYX-015 is not controlled by the p53 and p14(ARF) tumor suppressor genes.
abstract: The adenovirus mutant ONYX-015 is in phase III clinical trials as a novel antitumor therapy. Its apparent efficacy is thought to be due to its ability to replicate selectively in tumor cells defective in the signaling pathway for p53. Recent data have shown that p14(ARF), a positive regulator of p53, inhibits ONYX-015 replication in cells with a wild-type p53, a phenotype that characterizes normal cells. We, however, found that ONYX-015 activates p53 in tumor cells and in normal cells and that this can occur without p14(ARF) induction. We also show that ONYX-015 is not attenuated in cells with functional p53, whether or not p14(ARF) is expressed, and that where attenuation does occur, it is cell type specific.
authors.affiliation: Departments of Pathology, University of Otago, Dunedin, New Zealand.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Edwards
authors.forename: Brett R
authors.initials: BR
authors.lastname: Dix
authors.forename: Colleen J
authors.initials: CJ
authors.lastname: Myers
authors.forename: Deirdre
authors.initials: D
authors.lastname: Dobson-Le
authors.forename: Lily
authors.initials: L
authors.lastname: Huschtscha
authors.forename: Merilyn
authors.initials: M
authors.lastname: Hibma
authors.forename: Janice
authors.initials: J
authors.lastname: Royds
authors.forename: Antony W
authors.initials: AW
authors.lastname: Braithwaite
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF / Q000032:analysis / Q000235:genetics*; D014765:Viral Vaccines / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D025803:Tumor Suppressor Protein p14ARF; D014765:Viral Vaccines; C464532:dl1520