Development and Evaluation of Antibody Proteomics Technology for Rapid and Comprehensive Identification of Potential Biomarkers and Therapeutic Targets.

Abstract

Proteomics-based analyses are powerful means of identifying potentially useful proteins in the initial stage of drug development. Technological developments in the field of proteomics, and increases in the sensitivity of MS analyses, now facilitate identification and examination of increasingly small amounts of proteins that are differentially expressed in diseased versus normal tissues and can be candidate biomarkers or therapeutic targets. However, the current approach is for candidate proteins to be prioritized by research interest and then validated one by one; this is very inefficient. To address this issue, we have developed what we refer to as "antibody proteomics technology," which uses a phage antibody library and tissue microarray analysis to rapidly and comprehensively isolate monoclonal antibodies against candidate proteins for the identification of potential biomarkers and therapeutic targets. In our validation of this technology, we successfully identified oxysterol binding protein-like 5 and calumenin as potential biomarkers related to metastasis in lung cancer, annexin A4 as a potential biomarker related to cisplatin resistance in malignant mesothelioma, and Eph receptor A10 as a potential therapeutic target in breast cancer, including refractory breast cancer. These findings suggest that antibody proteomics technology has the potential to become a fundamental technology in drug discovery for the development of novel biomarkers and therapeutic targets.