ABSTRACT
Gene therapy is defined as a therapeutic approach that utilizes the introduction of a cloned gene, a gene fragment, or other nucleic material into tumor cells in order to modify the behavior of tumor cells or induce their death (1). As developments in cell and molecular biology have deepened our understanding of the mechanisms of apoptosis and cell cycle control, several genes have been identified which play key roles in maintenance of genomic integrity and regulation of the cell cycle. Alterations in specific genes have been associated with the development of sporadic or hereditary tumors and have been shown to affect tumor cell response to chemotherapy. This growing bulk of information has enabled the design of specific molecular strategies aimed at controlling tumor progression. Three fundamental approaches have been undertaken in cancer gene therapy. First, in the cytotoxic (or suicide) gene approach, the genes encoding enzymes, which transform inactive prodrugs into cytotoxic active drugs, are inserted into cancer cells. Only transfected cells expressing the specific enzyme become susceptible to killing. Second, corrective gene approaches are designed to combat observed alterations of specific genes involved in pathways controlling apoptosis and/or the cell cycle. Specific genes are introduced into tumor cells in order to cause cell cycle arrest, induce programmed cell death, or make tumor cells susceptible to conventional therapeutic agents such as chemotherapy and radiation. Third, immunopotentiating approaches introduce specific genes in tumor cells in order to enhance their recognition by the host immune system. Several approaches have emerged as potentially promising and some have already been tested in epithelial ovarian cancer.
