Gene Targeting to Hepatomas (AFP)

Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis worldwide, especially in eastern Asia and Africa (1). Recent advances in delivering genes to mammalian cells stimulate the possibility of gene therapy for human diseases, including cancer gene therapy (2). One approach of gene therapy for cancers is the transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene in tumor cells, because the killing effect of the HSV-tk product on the virus-infected cells is seen in only proliferating cells (3). HSV-tk can efficiently phosphorylate nucleoside analogs, and the phosphorylated products act as a chain terminator of DNA synthesis, leading to cell death (4). In addition, successful application of suicide gene therapy for cancer, in part, relies on the bystander effect, where the active chemotherapeutic agent produced in target cells diffuses from cells to neighboring malignant cells in sufficient concentrations to induce growth inhibition (5).