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Monitoring Phosphoproteomic Response to Targeted Kinase Inhibitors Using Reverse-Phase Protein Microarrays

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Phosphoproteomic networks mediated by protein kinases are the key drivers of proliferative and survival signals underlying human cancers, and as such a number of kinases have been the subject of intensive drug discovery efforts. A key question that must be answered during clinical development is whether a kinase inhibitor is effectively inhibiting its appropriate target kinase and pathway in the tumor. Reverse-phase protein arrays (RPMAs) offer the ability to analyze behavior of entire signaling networks in response to drug treatment and thus have promise as a technology for monitoring cellular response to kinase inhibitors. We have shown that it is possible to use RPMAs to detect phosphorylation changes in key multiple signaling pathway proteins in response to targeted inhibitors of EGFR, MEK, and PI3 kinase.
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