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Chemist cautiously optimistic about taxol synthesis

STANFORD -- Stanford chemistry Prof. Paul Wender expressed caution in interpreting a National Cancer Institute official's statement on Tuesday, March 17, that Wender's lab had "overcome the major hurdle in synthesizing taxol," the promising cancer drug that so far can be extracted only from the bark of the rare Pacific yew tree.

The Stanford group "has indeed overcome many hurdles in our efforts to synthesize taxol," Wender said. "We are in a final phase of our effort, but much more remains to be done." The statement was made by Bruce Chabner, associate director of NCI's Division of Cancer Treatment. He used Wender's research as one of several examples of progress in improving supplies of taxol. Chabner was quoted by Reuters News Agency after he spoke to reporters in Amsterdam, The Netherlands, at the opening of a joint U.S.-European symposium on new cancer drugs. Wender's lab has been aiming for total synthesis of taxol - putting the complex molecule together in the laboratory from basic raw materials, in a manner that will make it practical to produce the drug in large quantities.

So far, he said, the group has been able to produce most of taxol's three-ring core, and they are optimistic that they will be able to produce the entire molecule by the end of this year. "It's not unlike climbing Mount Everest," he said. "It's been a long climb, and we hope by the end of the year to scale up the face to the top."

But Wender said he was concerned about raising the hopes of cancer patients who might be treated with the scarce drug. "We are not at the point where we can fill bottles with it," he said. "Having a vision of what can be done, doing it in the laboratory and doing it in a practical way are three different steps. We are somewhere between step one and step two."

Wender will describe the research at an April 8 session of the American Chemical Society's national meeting in San Francisco. His report will be submitted for publication in a future issue of the Journal of the American Chemical Society.

His research is funded by the National Institutes of Health and by Bristol-Myers Squibb Co., which has exclusive rights to develop taxol in the United States.

Researchers in several universities and private companies are working to find ways to increase production of taxol in the laboratory or by using the needles of the Pacific yew. Harvesting the tree is controversial because it primarily grows in ancient forests that are the home of the endangered spotted owl. Currently it takes the bark of three full-grown trees to produce enough taxol to treat one patient. The drug has shown promise in clinical trials as a treatment for ovarian and breast cancer - patients with advanced ovarian cancer who failed to respond to standard therapies have reportedly shown a remarkable 35 percent response rate to taxol. It may be publicly available next year. However, with current production methods there is only enough taxol available for a fraction of the patients who potentially might be treated. Wender said this is what inspires his research group - ten postdoctoral and graduate students - to work around the clock and through weekends, to plant the flag on their metaphorical Everest. But he said, "I personally don't care who solves this problem, as long as it's solved. I just hope we will be in there." -jb-


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