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.
"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."
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.