Gene-directed enzyme prodrug therapy: a review of enzyme/prodrug combinations

Gene-directed enzyme prodrug therapy (GDEPT) is a promising, new, two-step treatment for cancer chemotherapy. In the first step, the gene for a foreign enzyme is administered and is directed to the tumour, where it is expressed by the use of specific promoters. In the second step, injected prodrugs are activated by the foreign enzyme. The design and synthesis of prodrugs able to undergo enzymatic activation in such systems is an essential component. This review focuses on the requirements which must be fulfilled by the components of GDEPT systems in order for this therapy to be considered a realistic possibility. A special emphasis is placed on the description of the prodrugs used in GDEPT protocols and the requirement for a bystander effect is also discussed.