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$4.37 million NCI grant accelerates recent laboratory finding in Ewing's sarcoma
Date:10/18/2010

sic enzymatic activity; one example is Gleevec, used for chronic myelogenous leukemia (CML). Torestsky believes his team's finding could provide a model upon which to design treatment for other disorders caused by the interaction between two proteins, and may be especially useful in cancers caused by translocations of genes, such as sarcomas and leukemias, the researchers say

In the United States, about 500 people are diagnosed each year with Ewing's sarcoma, and they are treated with a combination of five different chemotherapy drugs. Between 60 and 70 percent of patients survive over time, but with side effects from the treatment. Additional treatment options are available but without long-term potential for cure for patients whose cancer progresses, Toretsky says.

Discovery: A Long Journey

Torestky and his colleagues have chartered a 15-year path towards a new treatment for Ewing's sarcoma. Ewing's sarcoma is caused by the exchange of DNA between two chromosomes, a process known as a translocation. A new gene is created when the EWS gene on chromosome 22 fuses to the FLI1 gene on chromosome 11, and its product is the fusion protein EWS-FLI1 responsible for cancer formation. EWS-FLI1 is a good target for anticancer therapy since it is critical for the tumor and only present in tumor cells. It is a so-called disordered protein, which means it does not have a rigid structure. A number of cancer-causing proteins are disordered.

Previously, Toretsky and his colleagues were the first to make a recombinant EWS-FLI1 fusion protein. They used this recombinant protein to discover that the fusion protein stuck to another protein, RNA helicase A (RHA). RHA is a molecule that forms protein complexes in order to control gene transcription. "We believe that when RHA binds to EWS-FLI1, the combination becomes more powerful at turning genes on and off," says Hayriye Verda Erkizan, PhD, a postdoctoral researcher in Toretsky's lab.


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Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center
Source:Eurekalert

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