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Published on: September 19, 2018
Technology insight: pharmacoproteomics for cancer--promises of patient-tailored medicine using protein microarrays
Julia D Wulfkuhle1, Kirsten H Edmiston, Lance A Liotta
1Center for Applied Proteomics Molecular Medicine, George Mason University, Manassas, VA, USA. jwulfkuh@gmu.edu
Abstract:
Patient-tailored medicine can be defined as the selection of specific therapeutics to treat disease in a particular individual based on genetic, genomic or proteomic information. While individualized treatments have been used in medicine for years, advances in cancer treatment have now generated a need to more precisely define and identify those patients who will derive the most benefit from new-targeted agents. Cellular signaling pathways are a protein-based network, and the intended drug effect is to disrupt aberrant protein phosphorylation-based enzymatic activity and epigenetic phenomena. Pharmacoproteomics, or the tailoring of therapy based on proteomic knowledge, will begin to take a central role in this process. A new type of protein array platform, the reverse-phase protein microarray, shows potential for providing detailed information about the state of the cellular 'circuitry' from small samples such as patient biopsy specimens. Measurements of hundreds of specific phosphorylated proteins that span large classes of important signaling pathways can be obtained at once from only a few thousand cells. Clinical implementation of these new proteomic tools to aid the clinical, medical and surgical oncologist in making decisions about patient care will now require thoughtful communication between practicing clinicians and research scientists.
Insights
Personalized medicine uses genetic and proteomic data to tailor treatments. Reverse-phase protein microarrays offer a new way to analyze cellular signaling pathways for targeted cancer therapies.
Area of Science:
- Oncology
- Proteomics
- Genomics
Background:
- Individualized treatments are increasingly important in medicine, especially for cancer.
- Advances in targeted cancer therapies necessitate precise patient identification for optimal benefit.
- Cellular signaling pathways, driven by protein phosphorylation, are key targets for drug intervention.
Purpose of the Study:
- To highlight the role of pharmacoproteomics in tailoring cancer therapy.
- To introduce reverse-phase protein microarrays as a tool for analyzing cellular signaling.
- To emphasize the need for collaboration between clinicians and scientists for clinical implementation.
Main Methods:
- Utilizing proteomic knowledge to guide therapeutic selection.
- Employing reverse-phase protein microarrays (RPPMs) to analyze cellular circuitry.
- Measuring hundreds of specific phosphorylated proteins across signaling pathways from small biopsy samples.
Main Results:
- RPPMs can provide detailed proteomic information from limited patient samples.
- Simultaneous measurement of numerous proteins in key signaling pathways is feasible.
- This technology allows for a comprehensive view of cellular signaling states.
Conclusions:
- Pharmacoproteomics is poised to become central in personalized cancer treatment.
- RPPMs offer a powerful platform for analyzing patient proteomic profiles.
- Effective clinical integration requires strong communication between researchers and oncologists.
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