Selection of Cytochrome P450 Genes for Use in Prodrug Activation-Based Cancer Gene Therapy

Prodrug activation-based cancer gene therapy is a molecular strategy to improve the efficacy of cancer chemotherapy by conferring upon tumor cells the capability to metabolize specific anticancer prodrugs into lethal intracellular toxins. The overall goal of this strategy is to increase the generation of cytotoxic drug metabolites locally, at their site of action within the tumor. This therapy can provide for an increase in drug efficacy and potentially also a reduction in host toxicity, which may be achieved by a lowering of the therapeutically effective drug dosage, thereby reducing the need to expose host tissues to high cytotoxic plasma drug concentrations. This chapter describes the cytochrome P450-based prodrug activation strategy for cancer gene therapy , with a particular emphasis on the selection of suitable P450 gene/prodrug combinations.