Cisplatin-Sensitive breast tumors may be identified by molecular signature
Posted By Estudiante del Master de Inmunología On 30th Abril 2007 @ 07:50 In Investigación Biomédica, Master Inmunología | No hay comentarios
The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers.
Chee-Onn Leong, Nick Vidnovic, Maurice DeYoung, Dennis Sgroi, and [1] Leif Ellisen,
Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts, USA. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
[2] The Journal of Clinical Investigation 2007 Apr 19; [Epub ahead of print]
About two thirds of breast cancers contain receptor molecules for the hormones estrogen or progesterone, and in recent years antiestrogen drugs like tamoxifen have improved outcomes for women with those tumors. About 20 to 30 percent of tumors, some with hormone receptors, have elevated levels of a growth-promoting protein called HER2, and those tumors are candidates for treatment with the monoclonal antibody Herceptin. The third major subtype is the 15 to 20 percent of breast tumors that have neither estrogen nor progesterone receptors and also do not overexpress HER2.
Since these so-called triple-negative tumors are treatable with neither Herceptin nor antiestrogen drugs, the prognosis for patients with the tumors has been poor. Triple-negative tumors are the most common subtype found in patients with mutations in the BRCA1 gene, but they also appear in women without alterations in the so-called "breast cancer gene. There have been reports that BRCA1-associated, 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 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. These results suggest that testing p63 and p73 levels in patients; tumors might help predict whether they would benefit from cisplatin therapy.
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URL to article: http://blogs.creamoselfuturo.com/sanidad/2007/04/30/cisplatin-sensitive-breast-tumors-may-be-identified-by-molecular-signature/
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[1] Leif Ellisen: http://blogs.creamoselfuturo.com/sanidad/wp-admin/This%20paper%20describes%20a%2
0specific%20molecular%20pathway%20that%20makes%20these%20tumors%20sensitive%20to%20a%20therapy%20infrequently%20used%20for%20breast%20cancer,"%20says%20Leif%20Ellisen,%20MD,%20PhD,%20of%20the%20MGH%20Cancer%20This%20http:/www.pubmedcentral.nih.gov/picrender.fcgi?artid=1849987&blobtyp
[2] The Journal of Clinical Investigation: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=174
46929
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