Key protein may eradicate rare soft-tissue cancer

New York, Dec 30 (IANS): A rare soft-tissue cancer may be eradicated simply by inhibiting a key protein involved in its growth, research suggests.

Scientists have found that inhibiting the action of a protein called BRD4 caused cancer cells to die in a mouse model of malignant peripheral nerve sheath tumours (MPNSTs).

"This study not only identifies a potential new therapeutic target to combat MPNST, an incurable type of cancer that is typically fatal but also provides important insight into what causes these tumours to develop,” said Lu Le, assistant professor of dermatology at UT Southwestern Medical Centre and senior author of the study.

Researchers determined that BRD4, a bromodomain protein that binds to DNA to regulate gene activation, is expressed at an unusually high level in MPNST cancer cells.

When researchers inhibited BRD4 either genetically in the mice or pharmacologically by administering a compound called JQ1, the tumours began to shrink.

"These treatments suppressed tumour growth and caused the cancer cells to undergo cell death. This is why BRD4 inhibition is exquisitely effective against MPNSTs and may represent a paradigm shift in therapy for these patients,” said the study published in the journal Cell Reports.

MPNSTs are highly aggressive sarcomas that form around nerves. These tumours 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.

The five-year survival rate for MPNST patients is about 50 percent.

UT Southwestern is now working with a pharmaceutical company to develop a similar BRD4-inhibiting drug to launch a clinical trial for MPNST patients.



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