01912-A: Enhancing the Safety and Efficacy of Anti-Cancer Drugs in Dogs
Grant Status: Closed
The anti-cancer drugs doxorubicin and daunorubicin are used to treat a wide variety of cancers in dogs. The clinical utilization of these drugs is hampered by the development of cardiotoxicity in 69% of canine patients. Dr. Blanco will investigate a potential causative agent behind drug-related cardiotoxicity: the enzyme Carbonyl reductase 1 (CBR1). Dr. Blanco will perform a detailed kinetic characterization of canine CBR1 and determine whether this enzyme causes the production of cardiotoxic products when it acts on doxorubicin and daunorubicin in vitro. Dr. Blanco will also evaluate whether a new drug on the human market, MonoHer, inhibits the activity of canine CBR1, thus enhancing the safety of these drugs in dogs. Completion of this project will result in the first detailed kinetic characterization of this prominent canine drug metabolizing enzyme CBR1 and potentially identify a new drug that can be used to enhance the safety of two drugs currently used in canine cancer patients.
Ferguson, D. C., Cheng, Q., & Blanco, J. G. (2015). Characterization of the Canine Anthracycline-Metabolizing Enzyme Carbonyl Reductase 1 (cbr1) and the Functional Isoform cbr1 V218. Drug Metabolism and Disposition, 43(7), 922–927. https://doi.org/10.1124/dmd.115.064295
Quiñones-Lombraña, A., Cheng, Q., Ferguson, D. C., & Blanco, J. G. (2016). Transcriptional regulation of the canine carbonyl reductase 1 gene ( cbr1 ) by the specificity protein 1 (Sp1). Gene, 592(1), 209–214. https://doi.org/10.1016/j.gene.2016.08.005
Help Future Generations of Dogs
Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.