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Discovery of Novel Anti-tumor Antimitotic Agents That Also Reverse Tumor Resistance

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Scientists at Duquesne University and the Medical University of South Carolina report in the on line version of the Journal of Medicinal Chemistry (50, 3290, 2007) on novel compounds with potent anti-tumor activity, which are also active on cancer cells resistant to other anti-tumor agents. Many tumors develop resistance to chemotherapeutic agents such as taxol by producing protein pumps, such as p-glycoprotein, which expel various cancer drugs which penetrate into the cancer cell. Thus the level of cancer drug is reduced and the cancer cell escapes. The development of drug resistance is a critical event in cancer removing therapeutic options.

Detailed studies of the Duquesne compounds have shown that they, like Taxol and Vincristine, target tubulin which forms structural supports in the cell necessary for cell extension, migration and survival. The Duquesne compounds are not expelled by the pump protein, p-glycoprotein. Unexpectedly, it was discovered that the Duquesne compounds restored the sensitivity of drug resistant cancer cells to other anticancer agents by inactivating p-glycoprotein. Compounds with such dual actions, i.e. cytotoxicity and the ability to reverse drug resistance, are unusual. The significance of the work is that the development of resistance to previously effective cancer chemotherapeutic agents is a major cause of death in cancer patients and new more effective drugs are needed to treat patients with drug resistant tumors.

Dr. Aleem Gangjee, Distinguished Professor of Medicinal Chemistry at Duquesne University explained that “My group has been long interested in developing dual acting anticancer agents to enhance the effectiveness of cancer therapies. We have been successful in doing this with anti-folates, with anti-angiogenic agents and now with these anti-mitotic agents. We hope that this will start a new era in cancer research and hopefully treatment.”

Duquesne University is located in Pittsburgh PA and has broad educational programs in liberal arts , in science, in health science and in business.

Delphian Pharmaceuticals, a San Francisco biotech company, has licensed the Duquesne technology and is developing a portfolio of duel action anti-cancer compounds. President and CEO, Dr. Kumar Gadamasetti stated “ It is a pleasure to work with Dr. Gangjee and Duquesne in developing their platform of novel and promising therapeutic agents” He also noted that “Duquesne has one of the finest medicinal chemistry programs in the country.”

Dr. Kumar Gadamasetti can be reached at delphianpharma@aol.com