GENE-DIRECTED ENZYME PRODRUG THERAPY (GDEPT) - CHOICE OF PRODRUGS

Gene-directed enzyme prodrug therapy (GDEPT) is a two step gene therap y approach where the gene for a nonendogenous enzyme is directed to ta rget tissues. The enzyme is expressed intracellularly where it is able to activate a subsequently administered prodrug. It is a promising ne w treatment for cancer chemotherapy, The design and synthesis of prodr ugs able to undergo intracellular enzymic activation by foreign genes in such systems is an essential component. This review will focus on t he requirements to be fulfilled by the prodrugs used in this system. A special emphasis is placed on the description of the prodrugs (antime tabolites and alkylating agents) used in GDEPT protocols, The bystande r effect and its implications for the design of improved prodrugs for GDEPT is also discussed.