Profiling ER, PR, EGFR and HER2 in Breast Cancer Using Multiplex Tissue Immusta

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 like ly to respond to targeted therapies, including Herceptin. and novel tyrosine kinase inhibitors. 20/20 will utilize its proprietary Layered Expression Scanning (LES) technology. Transfer of antibody probes from a single tissue section to numerous bioaffinit y 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. During Phase II, we will demonstrate its tissue applicat ions with human breast tissue sections from clinical trials in breast cancer patients treated with growth factor and Akt inhibitors. Biomarker quantification will be standardized and calibrated to clearly demonstrate a clinical benefit in comparison with s ubjective visual estimation. 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 anticip ated 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 prot eins in both normal and phosphorylated form, in a single tissue section. PUBLIC HEALTH RELEVANCE:Our options for breast cancer diagnosis and treatment will be increasingly taking advantage of information obtained from tumor profiling assays, which will ind icate 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 studi es and drug trials, which will aim to invent novel treatment strategies using combinations of drugs that block growth factor' molecules.