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PI-103 Effective against Brain Cancer

According to the researchers at the University of California, San Francisco (UCSF) they have identified a class of compounds that prevents the growth of brain cancer. // The compound called the PI-103 acts as a potent drug candidate against lethal brain tumor. In animal studies (mice) with human glioma grafts the drug is found to be potent against proliferating cancer cells. The unique effectiveness of PI-103 stems from its ability to attack two separate steps in the series of signals that trigger the spread of cancer. The dual blockade proved to be a safe and effective inhibitor of cancer cell proliferation in mice with the human tumors, the scientists found.

The glioma research is being published online May 15 by the journal Cancer Cell. A description of the strategy used to identify the molecular level action of the inhibitors was published online by the journal Cell on April 27. Food and Drug Administration approval five years ago of the cancer drug Gleevec marked a promising new strategy against cancer. Gleevec was the first drug on the market designed to block ubiquitous signaling molecules called protein kinases – enzymes known to trigger normal cell proliferation, and in the case of cancer, the growth of tumors.

Another group of kinases, called lipid kinases are now emerging as important new targets, especially PI3 alpha kinase, an enzyme often found to be overactive in brain, breast, colon and stomach cancers. But the sheer number of related kinases – 15 in the PI3 kinase family alone – and uncertainty about how each acts in the body – has stalled progress. Broad spectrum drugs that inhibit many related kinases inevitably cause toxicity and are poor drug candidates. To overcome this hurdle, Kevan Shokat, PhD, a Howard Hughes Medical Institute investigator at UCSF, and Zachary Knight, a postdoctoral fellow in his lab, developed a strategy to systematically inhibit many different but related kinases to identify which ones might be prime t
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