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Bystander or no bystander for gene directed enzyme prodrug therapy.
Dachs, Gabi U; Hunt, Michelle A; Syddall, Sophie; Singleton, Dean C; Patterson, Adam V.
Afiliación
  • Dachs GU; Angiogenesis and Cancer Research Group, University of Otago, Christchurch, New Zealand. gabi.dachs@otago.ac.nz
Molecules ; 14(11): 4517-45, 2009 Nov 10.
Article en En | MEDLINE | ID: mdl-19924084
Gene directed enzyme prodrug therapy (GDEPT) of cancer aims to improve the selectivity of chemotherapy by gene transfer, thus enabling target cells to convert nontoxic prodrugs to cytotoxic drugs. A zone of cell kill around gene-modified cells due to transfer of toxic metabolites, known as the bystander effect, leads to tumour regression. Here we discuss the implications of either striving for a strong bystander effect to overcome poor gene transfer, or avoiding the bystander effect to reduce potential systemic effects, with the aid of three successful GDEPT systems. This review concentrates on bystander effects and drug development with regard to these enzyme prodrug combinations, namely herpes simplex virus thymidine kinase (HSV-TK) with ganciclovir (GCV), cytosine deaminase (CD) from bacteria or yeast with 5-fluorocytodine (5-FC), and bacterial nitroreductase (NfsB) with 5-(azaridin-1-yl)-2,4-dinitrobenzamide (CB1954), and their respective derivatives.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Profármacos / Terapia Genética Límite: Animals / Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2009 Tipo del documento: Article País de afiliación: Nueva Zelanda Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Profármacos / Terapia Genética Límite: Animals / Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2009 Tipo del documento: Article País de afiliación: Nueva Zelanda Pais de publicación: Suiza