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Taxol

TaxolŽ is a drug used in the treatment of cancer. It was discovered at Research Triangle Institute[?] (RTI) in 1967 when Dr. Monroe E. Wall[?] and Dr. Mansukh C. Wani[?] isolated the compound from the bark of the Pacific yew tree[?], Taxus brevifolia, and noted its antitumor activity in a broad range of rodent tumors. By 1970, the two scientists had determined the structure of Taxol, which is extremely complex. Taxol has since become an effective tool of doctors who treat patients with ovarian[?], breast and Kaposi's sarcoma cancers.

Unfortunately, the Pacific Yew is one the slowest growing trees in the world. Further, the treatment of just one patient requires the cutting down and processing of six 100-year old tress. This supply problem combined with the threat to a certain endangered owl species has prompted researchers to develop a bacterium (Streptomyces coelicolor[?]) that fermentatively produces a Taxol-like compound. 

Taxol, more properly known as paclitaxel, interferes with the normal function of microtubule growth. Whereas drugs like Colchicine[?] cause the depolymerization of microtubules in vivo, Taxol arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, Taxol binds to the tubulin protein[?] of microtubules and locks them in place. The resulting microtubule/taxol complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that Taxol induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2[?] (B-cell Leukemia 2) and thus arresting its function.

One common characteristic of most cancer cells[?] is their rapid rate of cell division. In order to accommodate this, the cytoskeleton of a cell undergoes extensive restructuring. Flexibility is key. Taxol is an effective treatment for aggressive cancers because it adversely affects the process of cell division by destroying this flexibility. Cancer cells are also destroyed by the aforementioned anti-Bcl-2 mechanism. Other cells are also affected adversely, but since cancer cells divide much faster than non-cancerous cells, they are far more susceptible to Taxol treatment.

The license to commercialize and market Taxol is held by the Bristol-Myers Squibb[?] Co., which was selected for this role by the U.S. National Cancer Instiute[?]. Bristol-Myers holds an exclusive contract in the harvesting of yew trees from US government lands; it has been criticized for having a "cancer monopoly". (1 - p.64)


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