title: Converting cancer genes into killer genes.
abstract: Over the past decade, it has become clear that tumorigenesis is driven by alterations in genes that control cell growth or cell death. Theoretically, the proteins encoded by these genes provide excellent targets for new therapeutic agents. Here, we describe a gene therapy approach to specifically kill tumor cells expressing such oncoproteins. In outline, the target oncoprotein binds to exogenously introduced gene products, resulting in transcriptional activation of a toxic gene. As an example, we show that this approach can be used to specifically kill cells overexpressing a mutant p53 gene in cell culture. The strategy may be generally applicable to neoplastic diseases in which the underlying patterns of genetic alterations or abnormal gene expression are known.
authors.affiliation: Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: L T
authors.initials: LT
authors.lastname: Da Costa
authors.forename: J
authors.initials: J
authors.lastname: Jen
authors.forename: T C
authors.initials: TC
authors.lastname: He
authors.forename: T A
authors.initials: TA
authors.lastname: Chan
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D005798:Genes, Bacterial; D016158:Genes, p53; D015316:Genetic Therapy; D006801:Humans; D007668:Kidney; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D009857:Oncogenes; D010957:Plasmids; D017354:Point Mutation; D011683:Purine-Nucleoside Phosphorylase / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D001616:beta-Galactosidase / Q000096:biosynthesis
chemical_list: D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D011683:Purine-Nucleoside Phosphorylase; D001616:beta-Galactosidase