Viral-mediated transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene has been demonstrated by several investigators to confer sensitivity to nucleoside analogs such as ganciclovir (GCV) in a variety of tumor cells including brain, prostate, bladder, kidney, ovary, head and neck, lung, pancreas, and liver cancers. Fourteen suicide gene clinical protocols using adenovirus vectors have been conducted, including four in prostate cancer. Two additional protocols for prostate cancer are in preparation in Japan and the Netherlands. A study conducted at Baylor College of Medicine was the first to demonstrate the safety of HSV-tk plus GCV therapy for human prostate cancer and the anticancer activity of gene therapy in this disease. However, it is still in the early stage of its development, with a number of problems to be overcome. Systemic delivery, specific introduction, and specific expression of the target gene are the major issues to be managed in order to establish a clinically relevant treatment strategy.
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