Chemical and pathway proteomics: powerful tools for oncology drug discovery and personalized health care.

ABSTRACT

In recent years mass spectrometry-based proteomics has moved beyond a mere quantitative description of protein expression levels and their possible correlation with disease or drug action. Impressive progress in LC-MS instrumentation together with the availability of new enabling tools and methods for quantitative proteome analysis and for identification of posttranslational modifications has triggered a surge of chemical and functional proteomics studies dissecting mechanisms of action of cancer drugs and molecular mechanisms that modulate signal transduction pathways. Despite the tremendous progress that has been made in the field, major challenges, relating to sensitivity, dynamic range, and throughput of the described methods, remain. In this review we summarize recent advances in LC-MS-based approaches and their application to cancer drug discovery and to studies of cancer-related pathways in cell culture models with particular emphasis on mechanistic studies of drug action in these systems. Moreover we highlight the emerging utility of pathway and chemical proteomics techniques for translational research in patient tissue.