Suicide gene therapy for urogenital cancer: Current outcome and prospects

Viral-mediated transfer of the herpes simplex virus thymidine kinase (HSV-t k) gene has been demonstrated by several investigators to confer sensitivit y to nucleoside analogs such as ganciclovir (GCV) in a variety of tumor cel ls 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 a nd 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 prost ate cancer and the anticancer activity of gene therapy in this disease. How ever, it is still in the early stage of its development, with a number of p roblems to be overcome. Systemic delivery, specific introduction, and speci fic expression of the target gene are the major issues to be managed in ord er to establish a clinically relevant treatment strategy.