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Genetic engineering could salvage once-promising anti-cancer agents

A group of anti-cancer agents that once produced dismal results in clinical trials could once again be a promising tool in fighting the deadly disease, thanks to research by a team of chemists at the University of Washington and in Germany.

The agents, called maytansinoids, were first discovered in the 1970s when scientists looked for tumor inhibitors in a rare Ethiopian plant. The same group of maytansinoids was later isolated from a new bacteria species. The compounds held great promise because of their exceptional potency, and early tests indicated they were effective against some tumors and leukemia lines.

But the compounds were difficult to come by in quantities large enough to manufacture drugs and, when potential treatments were developed, they proved too strong when tested in clinical trials.

"These compounds were too potent. They were toxic to patients," said Tin-Wein Yu, a UW research assistant professor of chemistry. "We thought if we could modify the chemical structure to make the agents more appropriate for cancer patients, that would be beneficial. And we could use the same strategy to ease the side effects."

UW researchers headed by Heinz Floss, an emeritus chemistry professor, teamed with researchers from Rheinische Wilhems-Universitt in Bonn, Germany, to develop ways of modifying genes that create maytansinoids and then produce cancer treatments that are more effective against tumors and better tolerated by patients.

Their efforts essentially relied on using the modified genes to produce the anti-cancer agent. The first step was to locate the genes that control maytansinoid formation and clone them. They first gained access to genes that control maytansinoid production, then altered the maytansinoid structure at the genetic level.

"If you can manipulate the production genes, it makes the process much easier," said Yu, who is the lead author of a paper describin
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Contact: Vince Stricherz
vinces@u.washington.edu
206-543-2580
University of Washington
10-Jun-2002


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