Suicide genes for gene therapy of cancer

The transfer of a suicide gene into tumor cells has been used as a novel therapeutic tool for cancer treatment. A suicide gene, such as the Herpes simplex thymidine kinase gene, can transform a prodrug into a compound that will be lethal for the tumor cell harboring the gene. Regardless of the method used to accomplish gene transfer, the tumoricidal activity of the suicide gene/prodrug system is not only due to the direct action of the modified prodrug inside the target cell, but also to the passive transmission of prodrug susceptibility to cells that are in close vicinity. This phenomenon, known as 'bystander effect', is partly dependent upon the presence of gap junction-mediated inter-cellular communications. However, mechanisms related to the immune system can also increase the bystander effect and, consequently, the antitumor efficacy of this therapeutic strategy. The feasibility of the suicide gene therapy has been shown in a variety of human cancers. Including tumors of the central nervous system, both by in vitro and in vivo studies and a number of clinical trials based on this approach are currently ongoing.