biological activity of Taxol. In 1966, the compound had been isolated from the bark of the Pacific Yew tree (Taxus brevifolia) as part of a concerted effort to find natural products that might cure cancer. At that time it was shown that Taxol was cytotoxic to cells growing in tissue culture, but over the next ten years there was almost nothing further gleaned about its biological action. However, within a few months of receiving her first samples of the compound, Dr. Horwitz with her then graduate student, Peter Schiff, found that Taxol, which had a unique chemical structure, inhibited cell division , which is deregulated in cancer, thereby promoting uncontrolled cell growth. In subsequent studies she showed that Taxol interferes with mitosis, the process whereby the chromosomes in the nucleus of a cell are duplicated and then segregated equally into two daughter cells.
"Susan's discovery that Taxol bound to and stabilized microtubules, thereby blocking cells in mitosis meant, in fact, that Taxol was a prototype for a new class of chemotherapeutic drugs. Susan recognized this immediately, and it was also quickly sensed by the NCI and others, who then moved Taxol into clinical trials and then pervasive clinical use," said Purpura.
The discovery of Taxol's unique structure and mode of action gave oncologists a new weapon in the fight against cancer. Dr. Horwitz found that unlike many of the cancer drugs that were approved or under development at the time, such as cisplatin and nucleotide analogs that interact with DNA, the mechanism of action of Taxol was not mediated by a direct interaction with DNA. Instead, she found that Taxol interferes with the normal functions of microtubules.
Microtubules are dynamic polymers, hollow cylindrical tubes that are constantly being remodeled by the addition or removal of tubulin subunits. During mitosis, microtubules act like long tethers to pull duplicate chromosomes to opposite poles of the cell so th
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Contact: john_lacey@hms.harvard.edu
public_affairs@hms.harvard.edu
617-432-0442
Harvard Medical School
22-Jun-2005
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