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    About 30,000 people will be diagnosed with kidney cancer this year and approximately 12,000 people will die from this disease. Unlike some other cancers, kidney cancer is not easily treated; it has a unique resistance to both chemical and radiation therapy.

    Recent research with gene therapy, however, holds promise that this new way of fighting cancer might be applied to kidney cancer. The study, conducted at New York Hospital and the University of Virginia, compared the effects of two forms of gene therapy on kidney cancer cells in the lab (in vitro) and in live mice (in vivo).

    Cytosine deaminase (CD) is an enzyme in the E. coli bacterium that converts a non-toxic substance called 5-FC to its toxic metabolite, 5-FU, which disrupts both DNA and RNA synthesis. The researchers called the combination of these two substances CD/5-FC. Thymidine kinase (TK), derived from herpes simplex virus, converts antiviral drugs like acyclovir (ACV) into analogs that disrupt DNA synthesis. The researchers called this combination TK/ACV. Disrupting DNA and RNA, the building blocks of reproduction in cells, is the aim of gene therapy.

    Another important aspect of gene therapy is the "bystander effect." This means that only a small percentage of cancer cells actually need to be infected by the toxic cocktail used, because these cells will in turn produce their own toxic metabolites that help kill cancer and shrink tumors. Thus, the greater the bystander effect created by a substance, the better that substance will be at fighting cancer.

    Genetically engineered versions of cytosine deaminase and thymidine kinase were created and combined with 5-FC and ACV, respectively. When applied to cancer cells in the lab, CD/5-FC killed significantly more than TK/ACV and produced a much stronger bystander effect.

    In mice infected with kidney cancer, the difference between the two combinations was much bigger. Only CD/5-FC showed any significant ability to kill cancer cells and prevent tumor growth. The researchers think this is because TK/ACV can't take advantage of the bystander effect and CD/5-FC can.

    Writing in "The Journal of Urology" recently, the researchers conclude that gene therapy based on cytosine deaminase should be investigated as "a powerful therapeutic modality for the treatment of metastatic [renal cell carcinoma]."



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