Abstract A200: Toward quantitative PI3K pathway PD analysis in clinical samples using an automated capillary electrophoresis-immunoassay platform.

Abstract

Abstract Here we report results of an independent evaluation of an automated capillary electrophoresis-immunoassay system for its utility in generating quantitative and reproducible pharmacodynamic (PD) biomarker data for the PI3K pathway using clinical specimens. Quantitative measurement of PD biomarkers associated with drug -target engagement in tumor tissue is an increasingly important part of evaluating new cancer therapies in early clinical trials. PD data are currently being used along with safety, pharmacokinetics, and efficacy data to make more informed clinical decisions regarding likelihood of success and progression of drugs into Phase II testing. Despite this increased focus, there are still very few assay platforms that support automated, reproducible and quantitative methods amenable to the small tumor biopsies available for these analyses. The Peggy™ (ProteinSimple) platform provides automated separation of proteins by size or charge and quantitation of analytes over a broad dynamic range from tissue samples using as little as 40 ng protein. Accompanied by the ability to process 96-samples in a single run, this platform is amenable to both pre-clinical and clinical PD determination. Our initial studies focused on evaluating the feasibility of developing a set of robust, quantitative PD biomarker assays that could be used systematically across our oncology portfolio to monitor the PI3K pathway. Here we present results for a panel of biomarkers associated with the PI3K pathway using cell lines and tumor xenografts in which we measured responses to drug treatments using AKT and mTOR inhibitors. Further, in a set of prospectively collected breast cancer core needle biopsies, we were able to detect baseline levels of these biomarkers. Taken together, these data suggest that this platform will be useful in quantitatively measuring changes in multiple PD biomarkers in a single tumor biopsy. Going forward, we propose to utilize this approach alone or in tandem with other immunoassay formats, such as immunohistochemistry, to provide greater insight into tumor biology and the effects of drug treatment following PI3K -AKT inhibition in the clinic to help inform important clinical decisions. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A200. Citation Format: Patricia E. Mccoon, Lourdes Pablo, Kristen McEachern, Emily Foster, Chris Womack, Lillian Castriotta, Jeff Brown, Carl Barrett. Toward quantitative PI3K pathway PD analysis in clinical samples using an automated capillary electrophoresis-immunoassay platform. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A200.