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Penn researchers identify potential target for breast cancer therapy
Date:12/22/2010

und that P-Rex1 is present in some breast tumors, particularly those that express the Her2/neu receptor or estrogen receptor and belong to the luminal subtype.

"We found that about two-thirds of the patient samples had very high levels of P-Rex1 expression in tumor cells in their lymph nodes," Kazanietz says. "There seems to be a correlation between P-Rex1 expression in the tumor cells and the capacity of these cells to metastasize. And since P-Rex1 is likely to be essential for cell migration and migration is essential for metastasis, we believe blocking this pathway could reduce the risk of metastasis."

P-Rex1 may be important for several other cancer-promoting pathways. For example, estrogen-receptor signaling also appears to rely on P-Rex1, which means that targeted inhibitors of P-Rex1 might improve responses to anti-estrogen therapies such as tamoxifen.

The authors also found that P-Rex1 is also used by another receptor, CXCR4, which has recently shown up in many cancer studies. Despite being used in numerous pathways during cancerous growth, P-Rex1 is not expressed in many normal tissues. "That gives us a very good target. It is really cancer specific," Kazanietz says. "What's more, as P-Rex1 is expressed in some subtypes of breast tumors, it may be an excellent prototype for future personalized medicine."

Preclinical data from other groups supports the importance of the Rac pathway in cancer, according to Kazanietz. And small molecule inhibitors that block proteins in the Rac pathway appear to have strong anti-cancer effects in model systems, though their use in patients still needs to be tested.


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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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