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Application of molecular technologies for phosphoproteomic analysis of clinical samples

Oncogene volume 34, pages 805–814 (2015)Cite this article

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Abstract

The integration of small kinase inhibitors and monoclonal antibodies into oncological practice has opened a new paradigm for treating cancer patients. As proteins are the direct targets of the new generations of targeted therapeutics, many of which are kinase/enzymatic inhibitors, there is an increasing interest in developing technologies capable of monitoring post-translational changes of the human proteome for the identification of new predictive, prognostic and therapeutic biomarkers. It is well known that the vast majority of the activation/deactivation of these drug targets is driven by phosphorylation. This review provides a description of the main proteomic platforms (planar and bead array, reverse phase protein microarray, phosphoflow, AQUA and mass spectrometry) that have successfully been used for measuring changes in phosphorylation level of drug targets and downstream substrates using clinical specimens. Major emphasis was given to the strengths and weaknesses of the different platforms and to the major barriers that are associated with the analysis of the phosphoproteome. Finally, a number of examples of application of the above-mentioned technologies in the clinical setting are reported.

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  1. Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA

    M Pierobon, J Wulfkuhle, L Liotta & E Petricoin

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All authors of this manuscript are inventors on US Government and University assigned patents and patent applications that cover aspects of the technologies discussed. As inventors, they are entitled to receive royalties as provided by US Law and George Mason University policy. All authors are consultants to and shareholders of Theranostics Health.

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Pierobon, M., Wulfkuhle, J., Liotta, L. et al. Application of molecular technologies for phosphoproteomic analysis of clinical samples. Oncogene 34, 805–814 (2015). https://doi.org/10.1038/onc.2014.16

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