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Development and Implementation of Clinical Proteomics for Precision Oncology Applications and Therapeutic Drug Development

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 patients that 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. We have now transitioned the reverse-phase protein microarray technology we originated in our laboratory into a functional clinical tissue based CLIA LDT assay, and have coupled this platform to laser capture microdissection to perform multiplexed mapping of the phosphoprotein-driven cell signaling networks that represent most of the direct drug targets of nearly all targeted therapeutics. Measurements of dozens to 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. This communication is beginning as proteomic analysis provide the treating physician with key missing pieces of information concerning selection of specific therapy(ies) tailored to the patient’s tumor activated protein “circuitry”.