Since its inception as a scalable and cost-effective method for precise quantification of the abundance of multiple protein analytes and post-translational epitopes across large sample sets, reverse phase protein array (RPPA) has been utilized as a drug discovery tool. Key RPPA drug discovery applications include primary screening of abundance or activation state of nominated protein targets, secondary screening for toxicity and selectivity, mechanism-of-action profiling, biomarker discovery, and drug combination discovery. In recent decades, drug discovery strategies have evolved dramatically in response to continual advances in technology platforms supporting high-throughput screening, structure-based drug design, new therapeutic modalities, and increasingly more complex and disease-relevant cell-based and in vivo preclinical models of disease. Advances in biological laboratory capabilities in drug discovery are complemented by significant developments in bioinformatics and computational approaches for integrating large complex datasets. Bioinformatic and computational analysis of integrated molecular, pathway network and phenotypic datasets enhance multiple stages of the drug discovery process and support more informative drug target hypothesis generation and testing. In this chapter we discuss and present examples demonstrating how the latest advances in RPPA complement and integrate with other emerging drug screening platforms to support a new era of more informative and evidence-led drug discovery strategies.
Keywords: Biomarkers; Drug combinations; Mechanism-of-action; Pharmacology; Phenotypic screening.