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Molecular signature may identify cisplatin-sensitive breast tumors

triple-negative tumors might be sensitive to cisplatin, a drug used to treat several other types of cancer, but whether the more common sporadic triple-negative tumors shared that sensitivity was unknown. The current study was designed to answer that question and to investigate the mechanism underlying cisplatin sensitivity.

The research team focused on the function of p63, a protein that plays a role in normal breast development and is related to the common tumor suppressor p53. They analyzed tissue samples from triple-negative breast tumors and normal breast tissues for the expression of several forms of p63 and another related protein called p73, known to promote the cell-death process called apoptosis.

The researchers found that a significant number of triple-negative tumors overexpress particular forms of p63 and p73, a pattern not seen in other types of breast cancers. Using an RNA interference system to inhibit the action of p63, they showed that the protein stimulates tumor growth by interfering with p73’s normal ability to induce cell death. Cisplatin was found to break up the binding of p63 to p73 and reactivate the cell-death process.

"The most important finding was that, if the tumor cells did not express both p63 and p73, the cells were not sensitive to cisplatin," says Ellisen. "These results suggest that testing p63 and p73 levels in patients?tumors might help predict whether they would benefit from cisplatin therapy." Ellisen is an assistant professor of Medicine at Harvard Medical School.

The clinical trial to investigate the role of p63/p73 expression in determining cisplatin sensitivity will be led by MGH researchers through the Dana-Farber/Harvard Cancer Center. Starting in Boston in the coming weeks, the trial will be open to patient with advanced triple-negative breast cancer and eventually will be offered at other U.S. cancer research centers. Patients or physicians interested in the trial s
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Source:Massachusetts General Hospital


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