Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

Camilla L Christensen, Torben Gjetting, Thomas Tuxen Poulsen, Frederik Cramer, Jack A Roth, Hans S Poulsen

    30 Citations (Scopus)

    Abstract

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1). Therapeutic effect was evaluated in vitro in SCLC cell lines and in vivo in SCLC xenografted nude mice using the nonviral nanoparticle DOTAP/cholesterol for transgene delivery.
    Original languageEnglish
    JournalClinical Cancer Research
    Volume16
    Issue number8
    Pages (from-to)2308-19
    Number of pages12
    ISSN1078-0432
    DOIs
    Publication statusPublished - 15 Apr 2010

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