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UW scientists find genetic pathway to potent anticancer agents

MADISON - Exploring the genomes of two different but related soil microbes, scientists from the University of Wisconsin-Madison have found the genes that govern the production of a class of highly potent anticancer agents.

Writing in two papers published this week (Friday, Aug. 16) in the journal Science, UW-Madison pharmaceutical sciences professors Jon Thorson and Ben Shen describe the discovery of genetic elements in soil-dwelling bacteria that are responsible for producing toxins that are among the most effective anticancer agents known.

The separate but complimentary findings portend the practical advent of a powerful new family of drugs to treat certain cancers.

"This molecule is so potent that it has to be directed to a particular target," says Thorson. "With this, all you need are one or two molecules and you can kill the (cancer) cell. These are different than most anticancer agents out there."

The genetic pathways found by Shen and Thorson produce chemicals known as enediynes. Discovered in the 1960s, scientists have long been intrigued by the potential of these natural toxins produced by soil bacteria. But enediynes' complicated chemical structure (first elucidated in 1985) and extreme reactivity have made them difficult to synthesize and use through conventional means.

The discovery of the genes that produce these agents means that enediynes can now be produced in quantity and their characteristics manipulated to make them far easier to use as therapeutic agents.

"We've found the genetic raw material to produce these compounds," Shen says. "With the genes in hand, we can take them apart and put them back together and that will allow improvements in production and development of new compounds" to treat cancer.

Working in two different species of soil bacteria -- one from North America and one from China -- Shen and Thorson found enediyne genetic pathways that are extremely similar, suggesting that
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Contact: Jon S. Thorson
jsthorson@pharmacy.wisc.edu
608-262-3829
University of Wisconsin-Madison
15-Aug-2002


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