Reverse Phase Protein Microarrays for Clinical Applications

Abstract

Phosphorylated proteins represent one of the most important constituents of the proteome and are under intense analysis by the biotechnology and pharmaceutical industry because of their central role for cellular signal transduction. Indeed, alterations in cellular signaling and control mechanisms that modulate signal transduction, functionally underpin most human cancers today. Beyond their central role as the causative components of tumorigenesis, these proteins have become an important research focus for discovery of predictive and prognostic biomarkers. Consequently, these pathway constituents comprise a powerful biomarker subclass whereby the same analyte that provides prediction and/or prognosis is also the drug target itself: a theranostic marker. Reverse phase protein microarrays have been developed to generate a functional patient-specific circuit “map” of the cell signaling networks based directly on cellular analysis of a biopsy specimen. This patient-specific circuit diagram provides key information that identifies critical nodes within aberrantly activated signaling that may serve as drug targets for individualized or combinatorial therapy. The protein arrays provide a portrait of the activated signaling network by the quantitative analysis of the phosphorylated, or activated, state of cell signaling proteins. Based on the growing realization that each patient’s tumor is different at the molecular level, the ability to measure and profile the ongoing phosphoprotein biomarker repertoire provides a new opportunity to personalize therapy based on the patient-specific alterations.