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Published on: September 19, 2018
Monitoring phosphoproteomic response to targeted kinase inhibitors using reverse-phase protein microarrays
Gabriela Lavezzari1, Mark R Lackner
1Theranostics Health, Rockville, MA, USA.
Abstract:
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.
Insights
Reverse-phase protein arrays (RPMAs) can monitor cancer drug effectiveness by detecting phosphorylation changes in signaling proteins. This technology helps confirm if kinase inhibitors are hitting their targets in tumors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Protein kinase pathways are crucial for cancer cell proliferation and survival.
- Targeting kinases with inhibitors is a major focus of cancer drug discovery.
- Confirming target engagement of kinase inhibitors in tumors is essential for clinical development.
Purpose of the Study:
- To evaluate Reverse-Phase Protein Arrays (RPMA) as a method for monitoring cellular responses to kinase inhibitors.
- To demonstrate the utility of RPMA in detecting drug-induced phosphorylation changes in key signaling pathways.
Main Methods:
- Utilized RPMA technology to analyze signaling networks in response to targeted drug treatments.
- Applied RPMA to detect changes in phosphorylation status of multiple proteins across different signaling pathways.
Main Results:
- Demonstrated the capability of RPMA to detect phosphorylation changes in response to kinase inhibitors.
- Successfully identified alterations in key signaling pathway proteins upon treatment with inhibitors of EGFR, MEK, and PI3 kinase.
Conclusions:
- RPMA is a promising technology for monitoring the effectiveness of kinase inhibitors in cancer.
- RPMA can provide insights into pathway modulation and target engagement in response to cancer therapies.
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