It will require further study to elucidate how they regulate the TRAIL pathway. The genes identified by this screen are likely to include novel therapeutic targets www.selleckchem.com/products/Perifosine.html that can be tested in combination Inhibitors,Modulators,Libraries with TRAIL in treating a variety of tumors, including breast cancer. Introduction The estrogen receptor status of breast tumors is the gold standard marker for predicting response to endocrine therapy. This is due primarily to its central role in estrogen signaling within ER breast cancer. However, ER status as currently measured does not accurately predict treatment response since at least 50% of ER tumors are de novo resistant to endocrine therapies such as tamoxifen, and many of those initially sensitive will acquire resistance despite the continued expression of non mutated ER in most cases.

ER, like many other proteins, can be post translationally modified. Post translational Inhibitors,Modulators,Libraries modifications such as Inhibitors,Modulators,Libraries phosphorylation, acetylation, methylation and Inhibitors,Modulators,Libraries ubiquitination of ER have been identified and in some cases shown to affect ER activity. Investigation Inhibitors,Modulators,Libraries of the relevance of phosphorylated forms of ER in vivo in human breast tumors revealed that many breast tumor biopsy samples have detectable phosphorylated ER. Recently, we determined expression of seven different phosphorylated residues on ER in breast cancer samples from patients who subsequently were treated with tamoxifen, and found that multiple tumors expressed combinations of phospho ER epitopes. We also established that detection of some of these phosphorylated sites was significantly associated with good and others with poor clinical outcome.

This led us to define an ER phosphorylation score which takes into account the presence of all seven inhibitor Imatinib phosphorylated ER epitopes detected in any one tumor. This so called P7 score was found to be significantly associated with overall survival from breast cancer death and relapse free survival in multivariate analysis. Such data support the hypothesis that a phosphorylation code for ER exists that is a more accurate prognostic and possibly treatment response marker than determination of expression of ER alone. It also suggests that ER is a central node at which integration of diverse signals occurs to regulate breast cancer growth and survival. We have hypothesized that the P7 score represents the balance of estrogen dependent and ligand independent ER signaling associated with any tumor. These data highlight the potential role played by kinases in breast tumors in vivo responsible for maintaining the ER phosphorylation code, as they may provide targets for development of new endocrine or alternative therapies.