Reverse phase protein microarrays and their utility in drug development.

The majority of human diseases, including cancer, are characterized by abnormal protein function. Proteins regulate virtually every cellular process and exhibit multiple kinds of post-translational modification that modulate expression levels and activation states, such as phosphorylation by protein kinases. Additionally proteins interact with each other in complex regulatory networks and signal transduction pathways modulated by feedback mechanisms. These pathways are disrupted in disease and altered by therapeutic drugs. Reverse phase protein microarray (RPMA) technology allows simultaneous measurement of numerous phosphorylated, glycosylated, cleaved, or total cellular proteins from complex mixtures in many samples at once. Therefore, RPMAs can provide a portrait of a cell's signaling pathways in diseased states, before and after treatment with drugs, and allows comparison of changes in drug-resistant and sensitive cells. Furthermore, the technology offers a means of connecting genomic abnormalities in cancer to targetable alterations in protein signaling pathways, even for genetic events that seem otherwise undruggable. Consequently, the RPMA platform has great utility in many steps of drug development including target identification, validation of a pharmaceutical agent's efficacy, understanding mechanisms of action, and discovery of biomarkers that predict or guide therapeutic response. RPMAs have become a powerful tool for drug development and are now being integrated into human clinical cancer trials, where they are being used to personalize therapy.