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Abstract
Grant Number: 1R43CA123994-01A2 Project Title: Profiling EGFR and Her2 in Breast Cancer using Multiplex Tissue Immunostaining
PI Information: Name Title JAMES, WILLIAM M. bjames@2020gene.com Abstract: DESCRIPTION (provided by applicant): We propose to develop a novel method and kit for profiling the expression and activation of signal transduction proteins in breast tumors. The goal is to create new "companion" diagnostics to better select patients likely to respond to targeted therapies, including Herceptin(r) and novel tyrosine kinase inhibitors. 20/20 will utilize its proprietary layered peptide array (LPA) technology. Transfer of antibody probes from a single tissue section to numerous bioaffinity membranes permits multiple target antigens (up to 50 if needed) to be assessed in a quantitative manner while preserving the local spatial orientation of the targets relative to the tissue section. The immediate goals are to develop a panel of 7 assays (comprising antigen-coated membranes and relevant antibodies), and to demonstrate their use for profiling AKT signaling in cultured breast cancer cells and archival tissues. During Phase II, we will demonstrate its tissue applications with animal models, and with human breast tissue sections from clinical trials in breast cancer patients treated with growth factor and Akt inhibitors. The product would have utility in both a research and clinical laboratory setting. Importantly, the system is open-ended to the addition of new prognostic markers and drug targets into the assay panel. There are several anticipated advantages of the layered membrane platform over current histopathology tools such as immunohistochemistry (IHC). These include conservation of tissue (such as for core needle biopsies) and the ability to simultaneously profile multiple signaling proteins in both normal and phosphorylated form. Our options for breast cancer diagnosis and treatment will increasingly take advantage of information obtained from tumor profiling assays, which will indicate customized therapies for each form of the disease. The novel diagnostic techniques to be researched will allow for microscopic profiling of tiny amounts of tissue for numerous cancer-causing molecules. There will be applications in pre-clinical studies and drug trials, which will aim to invent novel treatment strategies using combinations of drugs that block 'growth factor' molecules.
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Institution: 20/20 GENESYSTEMS, INC. 9700 GREAT SENECA HWY ROCKVILLE, MD 20850 Fiscal Year: 2007 Department: Project Start: 15-JUN-2007 Project End: 30-NOV-2007 ICD: NATIONAL CANCER INSTITUTE IRG: ZRG1