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Researchers create drug to keep tumor growth switched off
Date:2/11/2010

A novel and rapid anti-cancer drug development strategy has resulted in a new drug that stops kidney and pancreatic tumors from growing in mice. Researchers at the Moores Cancer Center at the University of California, San Diego, have found a drug that binds to a molecular "switch" found in cancer cells and cancer-associated blood vessels to keep it in the "off" position.

"We locked the kinase switch in the off position in cancer and in tumor-associated blood vessels," which differs from the way current inhibitors attempt to block active kinases, said David Cheresh, PhD, professor and vice chair of pathology at the UCSD School of Medicine and the Moores UCSD Cancer Center, who led the work.

The new approach employs scaffold-based chemistry combined with supercomputer technology, allowing for rapid screening and development of drugs that are more selective for the tumor. The development and screening processes were used to identify potential drug candidates able to halt a growth signaling enzyme, or kinase, which can foster tumor blood vessel and tumor growth. According to the researchers, the novel approach may become a useful strategy in cancer drug development. The study appears online the week of February 8, 2010, in the Proceedings of the National Academy of Sciences.

In this "rational design approach," Cheresh and his co-workers used the supercomputer at the San Diego Supercomputer Center to custom-design molecules that stabilized the inactive forms of two similar kinases, PDGFRβ and B-RAF both of which are found to be activated in tumors and in blood vessels that feed tumors. Since PDGFRβ and B-RAF work cooperatively, keeping both turned off causes synergistic effects in tumors, according to Cheresh.

"We custom design a drug for a target that we know either plays a role in blood vessel angiogenesis or tumor invasion," said Cheresh. "By doing this on the computer screen and effectively locking the
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Contact: Steve Benowitz
sbenowitz@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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