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UTSW study identifies potential therapeutic target for incurable, rare type of soft-tissue cancer
Date:12/26/2013

DALLAS Dec. 26, 2013 A deadly, rare type of soft-tissue cancer may be completely eradicated simply by inhibiting a key protein involved in its growth, UT Southwestern Medical Center researchers report.

In the study, published online today in Cell Reports, scientists found that inhibiting the action of a protein called BRD4 caused cancer cells to die in a mouse model of malignant peripheral nerve sheath tumors (MPNSTs).

"This study identifies a potential new therapeutic target to combat MPNST, an incurable type of cancer that is typically fatal," said Dr. Lu Le, Assistant Professor of Dermatology at UT Southwestern and senior author of the study. "The findings also provide important insight into what causes these tumors to develop."

MPNSTs are highly aggressive sarcomas that form around nerves. These tumors can develop sporadically, but about half of cases are in patients with a genetic disorder called neurofibromatosis type 1 (NF1) that affects 1 in 3,500 people. About 10 percent of NF1 patients will develop MPNST, which usually evolves from a benign but often large and disfiguring tumor called a plexiform neurofibroma.

Up to now, the preferred treatment for MPNST has been surgical removal, but that oftentimes is difficult or impossible due to the tumor's location around nerves. Radiation and chemotherapy are other options, but their effectiveness is limited. The five-year survival rate for MPNST patients is about 50 percent.

By studying changes in cells as they evolved into cancerous MPNSTs, researchers in Dr. Le's laboratory were able to determine that BRD4, a bromodomain protein that binds to DNA to regulate gene activation, is expressed at an unusually high level in MPNST cancer cells. This action caused another protein called BCL-2 to keep cancer cells from dying. Alternately, when researchers inhibited BRD4 either genetically in the mice or pharmacologically by administering a compound called JQ1
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Contact: Debbie Bolles
debbie.bolles@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

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