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New method to overcome multiple drug resistant diseases developed by Stanford researchers
Date:8/18/2008

substances through cell membranes. Working with Taxol(r), a widely used chemotherapeutic agent, they attached a series of arginines with their associated guanidinium groups and tried it out against Taxol-resistant ovarian cancer cells implanted in mice. It worked.

"It's an exciting result to be able to take a drug known to work against cancer, but stymied by resistant cells, and restore it to effectiveness using an arginine transporter," Wender said. "This bodes well for use with other drugs that succumb to resistance."

A paper describing the work is scheduled to be published next week in the online Early Edition of the Proceedings of the National Academy of Sciences. Wender's group collaborated with that of Chris Contag, a professor of pediatrics and of microbiology and immunology at Stanford's School of Medicine, who is a co-author on the paper.

"Overcoming Taxol resistance is big. It's huge," said Nelson Teng, professor of obstetrics and gynecology at the Medical School. "In essence, the technology can be used to overcome one of the most challenging types of problems of drug resistance."

The type of drug resistance that Wender's work has overcome develops when pumps located in the membrane that encloses a cell become sensitized to a medication. It is one of the most common ways in which resistance manifests. The pumps, which normally capture and eject foreign material from a cell, are produced at higher levels in certain resistant cells and, because of their increased number, become more effective at tossing the drug molecules out.

"It is kind of like a bouncer," Wender said. "If you're not recognized as being part of the club, then you're kicked out." Resistant cells also create a lot more of the pumps than a normal cell would have.

Some researchers have tried dealing with this situation by adding another molecule to the mix to inhibit the pump, keeping it busy so the medication can slip in while th
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Contact: Louis Bergeron
louisb3@stanford.edu
650-725-1944
Stanford University
Source:Eurekalert

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