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'Wrapping' Gleevec fights drug-resistant cancer

HOUSTON, May 1, 2007 -- A new study highlighted on the cover of this week's issue of Cancer Research finds that the anti-cancer drug Gleevec is far more effective against a drug-resistant strain of cancer when the drug wraps the target with a molecular bandage that seals out water from a critical area. The research appears as a priority report in the journal's May 1 issue.

The wrapping version of the drug known as WBZ-7 was created, produced and tested by three research teams, one headed by Ariel Fernandez from Rice University and the other two headed respectively by William Bornmann and Dr. Gabriel Lopez-Berestein from the University of Texas M. D. Anderson Cancer Center in Houston. The work sprang from a new collaborative partnership between the two institutions. In laboratory studies, WBZ-7 was found to be effective against a form of gastrointestinal cancer that has developed a resistance to imatinib, the drug sold under the brand name Gleevec.

Imatinib is one of the most effective of a new generation of cancer drugs that are designed to attack cancer cells and leave healthy cells unharmed. Imatinib targets a protein called KIT that plays a role in cell reproduction. In healthy cells, KIT is active only on rare occasions, but in some cancers the protein is always "on," acting as a biochemical catalyst that spurs cancer cells to constantly reproduce.

"The re-engineered version of imatinib accomplishes three things," said Rice bioengineering professor Ariel Fernandez, who designed the modified drug. "It binds with KIT. It binds with the most effective imatinib-resistant version of KIT. And finally, it binds in a way that ensures that any further version of KIT that becomes resistant to WBZ-7 will no longer be effective as a catalyst for cell reproduction."

Fernandez and his Rice colleagues postdoctoral researcher Alejandro Crespo and graduate student Xi Zhang developed the wrapping Gleevec variant WBZ-7. The wrapping p
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