Multiplexed quantitation of growth factor receptors and pathway activation in FFPE tumor tissue from the COIN trial

e14117 Background: The epidermal growth factor receptor (EGFR) is the target of antibody therapeutics, with cetuximab approved for use in metastatic colorectal carcinoma (mCRC) among other indications. While KRAS mutation is a negative predictor of cetuximab response, patients with wtKRAS may show low response rates through a number of resistance mechanisms. Co-expression of receptor tyrosine kinases, such as IGF1R or cMet, can confer resistance by providing alternative ways to activate tumor growth pathways. Additionally, current diagnostic assays cannot quantitate receptor or pathway activation in tissue. Characterization of these various resistance mechanisms are critical to maximizing response rates to EGFR targeted therapies. Methods: In order to address these issues, we used mass spectrometry to develop a multiplexed SRM (selective reaction monitoring) assay to measure levels of multiple protein targets on FFPE tumor tissue. These assays are based on the Liquid Tissue-SRM technology platform. This a...