Since conventional cancer treatments are not able to cure approximately 50% of cancers in patients, novel therapies must be developed. A number of different cancer gene therapy protocols are currently underway, including those using suicide genes. Gene therapy provides one approach by which tumors that are resistant to conventional agents may be treated. Inserting a suicide gene into tumor cells will lead to tumor cell death upon exposure to a prodrug, even in chemotherapy resistant tumor cells. One major limitation to using gene therapy for cancer is that modification of an entire tumor is not possible and untreated cells can grow back into tumors. However, the HSV-TK/GCV system has a critical advantage, since the gene-modified cells are toxic to nearby unmodified cells when exposed to the prodrug. This has been termed the “bystander effect”. Although the mechanism of this “bystander effect” is complex, the in vitro mechanism relies on transfer of toxic metabolites from gene-modified to unmodified cells, while the in vivo mechanism appears to be more complex and related to chemosensitization, hemorrhagic tumor necrosis, and activation of immune response.