Description: (Applicant's Description) The goal of the NCDDG is to develop a cancer treatment strategy based on the selective expression of a unique purine cleavage enzyme in tumor cells. The Biochemistry Program has 3 main objectives: The first is to verify and quantitate expression of enzymes delivered to tumors cells in vitro and in vivo by a variety of mechanisms in support of the gene delivery and in vivo efficacy studies; the second objective is to characterize the substrate characteristics of new purine cleavage enzymes to aid in the development of improved enzyme/prodrug combinations; and the third objective is to perform experiments to increase the basic understanding of the biochemical pharmacology involved with the activation of purine nucleosides in tumor cells. The goal of these studies is to fully characterize the biochemical pharmacology of purine nucleoside analogs that can be used as prodrugs. These studies will support the overall goal of the NCDDG by supplying the biochemical information that is necessary for the rational development of this strategy for the treatment of cancer.