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Muscling in on a deadly cancer

In a pair of new studies, University of Utah scientists took early but significant steps to fight a particularly deadly childhood muscle cancer by identifying some of the genetic events that cause the disease and then engineering mice that develop the tumors. The genetic events might be targets for new drugs that could be tested on the mice.

The disease, named alveolar rhabdomyosarcoma, "is a very mean childhood cancer," says study leader Mario Capecchi, co-chair of human genetics in the university's School of Medicine and an investigator with the Howard Hughes Medical Institute. "Once the cancer has spread, 80 percent of the children are likely to die within five years, even with the most aggressive treatment possible, including chemotherapy, surgery and radiation."

Capecchi says the studies provide evidence that the cancer may originate in mature or nearly mature skeletal muscle fibers. That is controversial because satellite stem cells cells that become new muscle long have been suspected of giving rise to rhabdomyosarcoma.

"If we know where it starts and the cause, you might be able to prevent it, detect it early or develop new treatments based on a better understanding of the biology of the tumor," says Charles Keller, a pediatric cancer specialist and first author of the studies.

During the past 30 years, "there have been dramatic improvements in cure rates for a number of cancers," he adds. "However, the outcome for advanced alveolar rhabdomyosarcoma has remained largely the same for 30 years."

Until now, scientists have been unable to breed mice with alveolar rhabdomyosarcoma, so "we understand the initiation and progression of this disease very poorly," Keller says. "This work represents a significant step forward in the understanding of the disease, and puts us on the path toward new therapies" less toxic to patients and better aimed at the cancer.

Keller and Capecchi believe it stil
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14-Oct-2004


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