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Why Cisplatin is Effective with Triple-Negative Breast Cancers

The cancerous cells of some individuals with breast cancer lack expression of two cell surface proteins, the estrogen and progesterone receptors, and do not express increased amounts of HER2. Individuals with such breast cancer (known as triple-negative breast cancer) do not respond to treatment with commonly used chemotherapeutic drugs and their prognosis is relatively poor.

But now, a new study from researchers at Massachusetts General Hospital Cancer Center, Boston, has indicated that triple-negative breast cancer cell lines are sensitive to exposure to the chemotherapeutic cisplatin.

In the study, which appears in the Journal of Clinical Investigation, Leif Ellisen and colleagues show that triple-negative breast cancer specimens express increased amounts of two proteins, delta-Np63 and TAp73. Delta-Np63 was shown to bind TAp73 and prevent it from killing the cancerous cells. Importantly, the chemotherapeutic drug cisplatin, but not other commonly used chemotherapeutic drugs, was found to release TAp73 from delta-Np63, causing the cells to be killed.

According to the authors, this study indicates that individuals with triple-negative breast cancer might benefit from early treatment with cisplatin if their cancerous cells express increased amounts of delta-Np63 and TAp73.

SOURCES:
Journal of Clinical Investigation, May 2007, published online April 17, 2007
Massachusetts General Hospital (http://www.mgh.harvard.edu)



 




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