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Blocking cancer in its path: New cellular defect discovered
Date:3/16/2010

ty, mTOR is considered "hyperactivated." This hyperactivation causes protein synthesis rates to climb. Cells begin to proliferate without limits and simultaneously become immortal, all of which leads to tumor formation.

"Our findings show that for a cancer cell, normal cellular functions such as protein synthesis can be specifically hijacked for tumor growth," explained first author Andrew Hsieh, a clinical fellow at the UCSF School of Medicine and the Department of Urology at the Helen Diller Family Comprehensive Cancer Center.

Ruggero said that the "dismal" clinical results seen with first generation mTOR inhibitor drugs like rapamycin "stemmed in part from the inadequate limit on unhealthy protein synthesis that is caused by hyperactivated mTOR."

Researchers in his laboratory made this key discovery through genetic tests that demonstrate that healthy genes in charge of protein production can become cancerous when mTOR is hyperactivated. To combat this, the scientists employed a new drug called PP242. This drug was discovered at UCSF in the lab of Kevan Shokat, PhD, Howard Hughes Medical Investigator and professor of cellular and molecular pharmacology at UCSF.

"This drug has shown promising results by bringing protein synthesis and cell proliferation levels back down to normal rates," Ruggero said. "In addition, PP242 helps fight the process of immortalization that cancer cells go through."

In their findings, PP242 proved to be more effective than similar drugs in its ability to jumpstart translational control in both live mice and human cells tested in the lab. PP242 is currently in Phase 1 clinical trials.

"We demonstrated that the drug kills the cancer cells more effectively because it blocks the abnormal production of proteins," said Ruggero. "The other drugs we tested did not show clinical effectiveness in blocking cancer development in this manner.''

The authors say that PP242 could become
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Contact: Elizabeth Fernandez
efernandez@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

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