Abstract 1948: Functional Profiling of Signal Transduction Pathway Proteins in Gastric Cancer (GC) Patients

Abstract Although gastrectomy is the only curative treatment in gastric cancer (GCA) patients, a high recurrence rate ranging from 40 ∼ 60% following curative surgery still accounts for poor overall survival. In order to further improve survival, there is an urgent need to identify reliable molecular prognostic markers for survival or recurrence following adjuvant chemoradiation therapy. With the advent of molecularly targeted therapy in cancer care, profiling of pathway proteins for targeted drug is of utmost importance. Hence, we have developed a multiplexed immunoassay platform for functional profiling of the signal transduction pathway proteins using a multiplexed immuno-microarray platform. A multiplexed protein microarray platform, Collaborative Enzyme Enhanced Reactive-immunoassay (CEER) that utilizes the formation of a unique immuno-complex requiring co-localization of two detector-antibodies (d-abs) has been utilized to profile targetable biomarkers in 447 fresh frozen tumor tissues procured during surgical procedure from GCA patients with localized disease. The collaboration between two channeling-enzymes conjugated on two d-abs in proximity enables the profiling of the target proteins with extreme sensitivity and specificity in multiplexed fashion. As CEER can also be configured for each specific target protein, it allows differential detection of truncated targets (i.e., p95HER2) from their normal counter parts (i.e., HER2). Here we report the profiling of HER2, p95HER2, HER1, HER3, PI3K, cMET, Shc and IGF1R in GCA for their levels of expression and phosphorylation. Approximately 12% of patients in this cohort expressed high levels of HER2. Varying levels of truncated HER2 were detected in 7.1% (27/447) of GCA pts. HER3 were found in approximately 40% of pts. The prevalence of biomarker expression/activation along with the outcome of unsupervised clustering analysis of signaling molecules revealing diverse and distinct disease subtypes will be presented. The treatment of recurrent or metastatic GC may be optimized based on patient-specific functional profiling of biomarker leading to patient-tailored treatment strategies. In addition, the incidence of alteration in transduction pathway proteins may guide oncologists for further clinical development of targeted therapies or combined / sequenced targeted therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1948. doi:10.1158/1538-7445.AM2011-1948