Chemotherapy targets diseased and healthy cells causing nausea, immune suppression, gastric ulceration, secondary tumorigenesis and alopecia. Furthermore, some types of cancer (such as pancreatic) mean certain death for the patient. There is a need for drugs and therapies that selectively target tumor cells, treat previously untreatable tumors and maintain low toxicity when administered to patients.
Solution
Administering a selective radio-sensitizing or chemotherapeutic agent to tumors could achieve all of these goals. For tumors with high levels of cytidine deaminase, such as pancreatic tumors, this elevation provides a therapeutic approach with novel pro-drugs that require deamination for their activation. For tumors with high levels of uridine/cytidine kinase, a different class of novel pyrimidine analogs can be activated selectively in tumors for a therapeutic advantage.
Competitive Advantage
There is no treatment other than classic chemotherapy which has been ineffective in treating this disease.
Applications
(1) Pancreatic and colo-rectal cancer for those tumors with high levels of cytidine deaminase;
(2) Breast, lung, colo-rectal and brain tumors for those tumors with high levels of uridine/cytidine kinase.
Patent Status
International Patent Application No.
WO2008085611
entitled "DESIGNER THERAPHY OF PANCREATIC TUMORS" was published on July 17, 2008.
Licensing Opportunity
The University of Miami is seeking collaborative research and licensing options.
About the Inventors
Dr. Sheldon Greer, Professor of Microbiology & Immunology, Biochemistry & Molecular Biology and Radiation Oncology has been engaged in studies of pyrimidine metabolism as related to Chemotherapy and Radiation Therapy of Cancer Patients. Dr. Greer obtained his Ph.D. at Columbia University and did his Post Doctoral work at Columbia College of Physicians and Surgeons for 6 years. It was there that he discovered the Radio-sensitization of cells by 5-Bromouracil and 5-Iodouracil. He also discovered a mechanism by which cells age and give rise to cancer: Depurination.
Dr. Greer has been at the University of Miami, Miller School of Medicine since 1961 where he demonstrated the effectiveness of the novel prodrug 5-fluoro-2'-deoxycytidine which is now being developed by the NIH as an effective hypomethylating agent for the treatment of cancer. More recently, he discovered the hypomethylating drug, Zebularine.
Dr. Greer has also developed a second generation radiosensitizing drug, Cytochlor. The NIH contracted studies in primates in which Cytochlor was given 5 days/week for 3 weeks with no clinical signs of toxicity. The drug is now in a Phase I Clinical trial. While engaged in studies of tumors and associated normal tissue of 220 patients with cancer of the head and neck, colon/rectum, brain, lung, breast and most recently, pancreas, with respect to 4 enzymes of pyrimidine metabolism, a surprising dramatic discovery: 90% of the 40 pancreatic tumors examined displayed pronounced elevation of only one of the four enzymes, cytidine deaminase (CD). 60% and 40% of the patients had a >4- and >6-fold, respective increase in the enzyme above that of adjacent normal tissue. No other tumor displayed this marked elevation, which can be exploited for a therapeutic advantage with 5 novel deoxyribonucleoside analogs, never before used in the clinic. Three are Radiosensitizers and two are Chemotherapeutic Agents. Three of the five were custom synthesized for Dr. Greer.
Selected References
Cheng, J.C., Yoo, C.B., Weisenberger, D.J., Chuang, J., Wozniak, C., Liang,G., Marquez. V.E., Greer, S., Orntoft, T.F., Thykjaer, T. and Jones, P.A. Preferential Responses of Cancer Cells to Zebularine. Cancer Cells, in press, 2004.
Cheng, J., Matsen, C., Gonzales, F., Greer, S., Marquez, V., Jones, P., Selker, E. A Novel Inhibitor of DNA Methylation , Zebularine, Can Reactivate Silenced Genes in Human Cancer Cells. Journal National Cancer Institute 95:399-409 (2003).
Greer, S., Wozniak, C., Arnold, D., Thurer, R., Agarwal, R. and Mian, A. Pyrimidine Metabolizing Enzyme-Driven Cancer Chemotherapy, Radiation Therapy and Selective Rescue. Miami Nature Biotechnology Winter Symposium 14:55 (2003).
Greer, S., Alvarez, M., Mas, M., Wozniak, C., Arnold, D., Knapinska, A., Norris, C., Burk, R., Aller, A., and Dauphin￩e, M. Five-chlorodeoxycytidine, a Tumor-selective Enzyme Driven Radio-sensitizer, Effectively Controls Five Advanced Human Tumors in Nude Mice. Int. J. Rad. Oncol.Biol.Phys. 51: 791-806 (2001).
