Abstract 5537: Quantitative multiplexed SRM analysis of oncogenic receptors in FFPE colorectal carcinoma tissue

Abstract

Abstract Multiple receptor tyrosine kinases are the target of either approved drugs (Her2, EGFR) or robust clinical development efforts (cMet, IGF1R, Her3, etc). In many cases initial drug response is followed by resistance and tumor progression. There are many mechanisms which have been proposed for this including co-expression of alternate RTKs that continue to stimulate tumor growth in the presence of EGFR/Her2 inhibition. Because of the potential that co-expression of oncogenic receptors mediates resistance in these clinical trials, we have developed a panel of new SRM assays which measure the expression of these critical RTKs in multiplex from FFPE tissues. These assays are based on the Liquid Tissue®-SRM technology platform. This approach enables relative and absolute quantification of proteins and their phosphorylation status directly in formalin fixed paraffin embedded (FFPE) tissue. Here we describe the quantitative multiplexed analysis of EGFR, IGF1R and cMet expression in a cohort of 75 archival FFPE colorectal cancer tumors from Cetuximab treated patients. This analysis identified 7 different fingerprints of expression of these three targets. Since each of these targets has either approved inhibitors, or highly active clinical development programs, we are hopeful that this analytical approach can help to identify patients who are most likely to respond to single or combination therapies of RTK inhibitors Follow up studies are underway to expand the RTK- multiplex, repeating EGFR, IGF1R and cMet and adding Her2, Her3, Her4, DR5, cSrc, and other drug targets into the multiplex. Our intention is to use this broader multiplex to re-analyze these patients and attempt to correlate the multiplexed expression of these targets with drug response data. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5537. doi:1538-7445.AM2012-5537