A potential target for breast cancer therapy has been identified by researchers.
Overexpression or hyperactivation of ErbB cell-surface receptors drives the growth of many breast cancers. Drugs, like Herceptin, that block the receptors' signals halt tumor progression in some patients.
However, not all patients' tumors respond, with some becoming resistant over time. Different drugs that interfere with other steps in the signaling pathway may improve the response of patients, yet little is known about these molecules.
Now, Marcelo G. Kazanietz, professor of Pharmacology at the University of Pennsylvania School of Medicine and colleagues, report that a protein called P-Rex1 is crucial for signal transmission from ErbB receptors.
They found that P-Rex1 is overexpressed in nearly 60 percent of breast cancer samples tested and patients whose tumors express P-Rex1 were more likely to develop metastasis, compared with those whose tumors did not express P-Rex1.
The team also found 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.
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 team's research is featured on the cover of the December 22 issue of Molecular Cell.