Research Focus
Using gene transfer, RNA interference, and gene knockout technologies, we are investigating the metabolic pathways and molecular mechanisms affecting antitumor activity and tumor selectivity of cytotoxic agents, fluoropyrimidines and anthracyclines. For clinical translation, we are exploring rapid, easy methods to monitor the activity of the metabolic pathways and effectors of fluoropyrimidines and anthracyclines. As a final goal, our research will provide evidence and methodologies for the individualization of these chemotherapeutic agents. Using these gene-targeting technologies, we are also investigating the biological function of human aldose reductase-like-1 (AKR1B10) and its role in cancer development and therapy.

Selected Publications
Pizzorno, G, Cao, D, Leffert, J. J, Russell, R. L, Zhang, D, and Handschumacher, R. E. Homeostatic control of uridine and the role of uridine phosphorylase: a biological and clinical update. Biochim. Biophys. Acta. 1587(2-3): 133-144, 2002 Pub Med

Cao, D, and Pizzorno, G. Uridine phosphorylase: An important enzyme in pyrimidine metabolism and fluoropyrimidine activation. Drugs of Today. 40(5): 431-443, 2004 Pub Med

Cao, D ., Leffert, J. J., McCabe, J., Kim, B., and Pizzorno, G. Abnormalities in uridine homeostatic regulation and pyrimidine nucleotide metabolism as a consequence of the deletion of the uridine phosphorylase gene. J. Biol. Chem. 280(22): 21169-21175, 2005 Pub Med

Wan, L., Cao, D., Zeng, J., Yan, R., Pizzorno, G. Modulation of uridine phosphorylase gene expression by tumor necrosis factor-{alpha}enhances the antiproliferative activity of the capecitabine intermediate 5'-Deoxy-5-fluorouridine in breast cancer cells. Mol. Pharmacol. 2006 Jan 5

Cao, D., McCabe, J., Yan, R., Wan, L., Zhao, G., Kim, B., and Pizzorno, G. and Pizzorno, G. Improvement of antitumor efficacy of fluoropyrimidine by tumor-specific modulation of uridine phosphorylase activity. In Press.