Functional Proteomic Analysis of Signaling Networks and Response to Targeted Therapy

Abstract : The purpose of the research done has been to determine the regulation of the EGFR network and identify how manipulations of the network alter signal flow to bypass targeted inhibitions. The scope of the project is to understand the network and determine which molecules have to be targeted to inhibit tumor cell proliferation. The major finding thus far are 1) We have performed the proteomic analysis of the signaling network in a panel of 4 breast cancer cell lines and determined the network response to EGF and targeted inhibitors. 2) We have determined how information flows within the network and feedback regulation. 3) Using these biological data we have developed a computational model and have made predictions to identify combinations of targets. 4) We have experimentally tested the predictions on two cell lines with different mutations. We have completed the tasks listed for this time period and are on track as indicated in the original grant.