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Therapeutic Target for Deadly Childhood Muscle Cancer Identified

by Rajashri on August 17, 2008 at 12:28 PM
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 Therapeutic Target for Deadly Childhood Muscle Cancer Identified

A new study from The University of Texas Health Science Center at San Antonio and partner institutions has revealed that curbing the activity of a substance called "platelet-derived growth factor receptor A" dramatically reduced aggressiveness of an often-untreatable childhood muscle cancer in mice and cells

Childhood muscle cancers, also called rhabdomyosarcomas, are the most common soft tissue sarcomas of childhood. The alveolar subtype is particularly difficult to treat because at diagnosis more than half of the children have lymph node involvement or distant metastasis (spread), the authors wrote.

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"The way this disease grows and spreads has perplexed clinicians and researchers for nearly three decades, during which time the dismal outcome for metastatic alveolar rhabdomyosarcoma has remained essentially unchanged despite improvements in surgical technique, radiation delivery and chemotherapy," said co-author Charles Keller, M.D., assistant professor of Cellular and Structural Biology at the Greehey CCRI.

The cure rate for the metastatic form is estimated to be 20 percent or lower. Dr. Keller said the findings offer a promising avenue for improving that outcome. "A therapeutic strategy for children with muscle cancer might be developed that would target this growth receptor and possibly similar ones at the same time," he said. "The benefit to the patient is that such treatments are clinically available today for adult cancer patients who have other diseases. Importantly, too, the way these targeted therapies work is less toxic than chemotherapy."
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The researchers studied genetically engineered mice with tumors that develop the mutations, and frequent metastases, inherent to alveolar rhabdomyosarcomas. Dr. Keller developed this specialized mouse tumor model while training in the laboratory of 2007 Nobel Laureate Mario Capecchi, Ph.D., at the University of Utah.

In the current study, assays performed in the Keller laboratory by postdoctoral trainee Eri Taniguchi, Ph.D., showed that platelet-derived growth factor receptor A, and two proteins that mediate its effects, were highly activated in both the primary and metastatic tumors.

Using three different methods to dampen the platelet-derived growth factor receptor, the scientists noted significant reduction of tumor cell growth both in the mice and in cell cultures.

"We believe this clearly establishes platelet-derived growth factor receptor A as a potential future therapeutic target in alveolar rhabdomyosarcoma," Dr. Keller said.




Source: Newswise
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