EC Pharmacology and Toxicology

Several decades ago, we at the University of Minnesota, initiated studies to explore cell signaling mechanisms, that modulate the physiology/pathology, functions/dysfunctions, at cellular, tissue, and organ levels. We used a variety of molecules, to study the process at the ultrastructure level, as well as at biochemical, and molecular levels [1,2]. Our department, (Laboratory Medicine and Pathology) also organized, one of a kind course on ‘Mechanisms of Diseases.” In our exploratory studies, we used several molecules such as Vincristine, Cytochalasin, Colchicine, Taxol, Calmodulin, Amiloride, and calcium ionophore, A23187 [3-12]. Little did we know at that time, that some of these molecules, will become major anti-cancer drugs. Drug discovery and development takes a fairly long process. For instance, Paclitaxel (Taxol), the most well-known natural-source cancer drug was collected by USDA in 1962, yet it took decades until 1977 for the National Cancer Institute (NCI), to confirm antitumor activity in the mouse melanoma model. It took another decade for NCI, to begin phase one clinical trial of Taxol, against a number of cancer types. In December 1992, the FDA approved Taxol for the treatment of ovarian cancer. In 1994, the FDA approved Taxol for use against breast cancer. Vinca alkaloids are administered with cyclophosphamide, doxorubicin, prednisone, methotrexate, procarbazine, and dacarbazine. The limitation of vincristine therapy is its neurotoxicity [13,14]. In the early 90s, most drugs used in cancer treatment worked by killing cells, that were in the process of replicating their DNA, and dividing to form new cells.

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