Abstract 3497: Pathway profiling for personalized medicine: Comparison of two immunoassays.

Abstract

Abstract Cancer therapy is evolving to a detailed molecular analysis of the patient's tumor followed by treatment with selective drug(s) targeting the individual properties of the tumor based upon identification of prognostic and predictive biomarkers. This requires comprehensive, highly sensitive test systems. We therefore sought to develop a sensitive diagnostic test for functionally profiling a spectrum of signaling pathway proteins in tumor samples. Here, we evaluated and compared two assay platforms: CEER (Collaborative Enzyme Enhanced Reactive-Immunoassay; Prometheus Labaratories) and MSD (Meso Scale Discovery). Breast, lung, and prostate cancers as well as glioblastoma and melanoma model cell lines (in all 10 cell lines) with various oncogenic pathway signatures were treated with different concentrations of PI3K inhibitor (BAY 806946) or an inhibitor targeting HER1 and HER2 (Lapatinib). Cells were lysed and the activation status as well as abundance of ten pathway proteins (HER1, HER2, cMET, PI3K, AKT, ERK, MEK, PRAS40, RPS6, and P70S6K) was measured by MSD at Bayer in Berlin and by CEER in a blinded fashion at Prometheus Laboratories. Target-specific inhibition (IC50) and downstream signal modulations were determined and compared. Overall we found a high concordance between the two assays. While target specific inhibitions were observed in relevant cell lines, varying mechanisms of treatment resistance due to redundant pathway activation, feedback loop or pathway cross talks were observed between the PI3K/AKT and RAS/ERK pathways. This study shows that sensitive immunoassays are a suitable tool for the detection and monitoring of biomarkers and provides new insights into the mode of action of targeted agents. Comprehensive profiling of signaling pathways holds promise as an approach to personalize selection of anticancer therapy. Citation Format: Antje Stresemann, Oliver von Ahsen, Oliver Politz, Phillip Kim, Sharat Singh, Khusru Asadullah, Karl Ziegelbauer, Thomas Krahn. Pathway profiling for personalized medicine: Comparison of two immunoassays. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3497. doi:10.1158/1538-7445.AM2013-3497