Adenovirus-Mediated Targeted Gene Therapy for Breast Cancer and for Purging Hematopoietic Stem-Cell Sources

Gene therapy provides a potentially powerful approach for cancer treatment. One strategy is based on direct transfer of a suicide gene, which encodes enzymes that can activate a prodrug within tumor cells and thereby render the tumor cells sensitive to agents that are otherwise nontoxic to the cell. For example, introduction of the herpes simplex virus thymidine kinase gene (HSV-tk ) or the bacterial cytosine deaminase (CD) gene, which respectively render mammalian cells sensitive to the otherwise nontoxic antiviral agent ganciclovir (1 ,2 ) and to the antifungal drug 5-fluorocytosine (3 ,4 ). Another novel prodrug activation system is the activation of conventional anticancer prodrug cyclo-phosphamide and ifosphamide by intratumor expression of mammalian cyto-chrome P450 , such as rat 2B1 or human 2B6 to further sensitize cancer cells (5 ,6 ). Whereas gene therapy may provide a new therapeutic approach, clinical efficacy will require gene delivery systems, which possess both high gene-transduction efficiency and target-cell specificity.