Prodrug/drug sensitivity gene therapy: current status.

The prodrug strategy has its own particular real and theoretic obstacles. Clinical strategies and research efforts have tried to approach these problems. The bystander effect, whereby nontransduced cells are affected by simple proximity to those that have received the novel gene, has enabled many prodrug systems to be more efficient than anticipated. Several prodrug gene therapy systems have been developed, including the HSVtk/GCV and CD/5-FC systems. Preclinical work serves as the foundation for clinical trials examining the use of prodrug gene therapy systems. At least 21 prodrug gene therapy trials have been approved for patient enrollment in the United States and Europe. Recent work has demonstrated the success of prodrug gene therapy, which might lead to combination therapies using vector transfer of both prodrug/suicide as well as immune-enhancing genes to tumors.