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Compound that blocks sugar pathway slows cancer cell growth
Date:11/18/2010

r of Neurosurgery Research and Ludwig Collaborative Laboratory Director at Johns Hopkins.

Riggins identified BPTES' anticancer potential after screening many compounds for their glutaminase-blocking activity. BPTES was developed at Hopkins' Brain Science Institute as a potential treatment for neurological disorders and injuries that damage brain cells.

Although BPTES itself may not be useful as a therapy because of solubility problems, says Riggins, scientists at Johns Hopkins' Brain Science Institute are creating new versions of it that may overcome the problem.

"We can envision a day when patients who have IDH1 mutations are given a glutaminase inhibitor in addition to therapies that target other genomic aspects specific to their cancer," says Dang.

The mutation in IDH1, which stands for isocitrate dehydrogenase 1, was first spotted in 2008 in results from a genomewide scan of brain cancers led by Johns Hopkins scientists. It is now linked to more than 70 percent of three common types of gliomas: low-grade astrocytomas, oligodendrogliomas, and secondary glioblastomas. Researchers also have found mutations in acute myelogenous leukemias.

The mutation occurs within a single spot along a string of thousands of genetic coding letters. Among previous findings led by Johns Hopkins, patients with IDH1 mutations appear to survive at least twice as long as those without them. The researchers estimate that some 6,000 adults and children with brain cancer per year in the United States could have IDH1 mutations.

Dang and Riggins plan to test glutaminase inhibitors in cell cultures of other cancers and eventually combine the inhibitors with other gene "targeted" therapies in animal and human tests.

Both investigators also are co-inventors on a patent application on using glutaminase inhibitors for cancers with IDH1 mutations. Dang and researcher Joshua D. Rabinowitz from Princeton University are consultants
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Contact: Vanessa Wasta
wasta@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
Source:Eurekalert

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