Why cisplatin kills breast cancer cells when other drugs fail
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 online on April 19 in advance of publication in the May print issue of 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. 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.
TITLE: The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers
Leif W. Ellisen
Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts, USA.
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