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Reverse Phase Protein Microarrays and Their Utility in Drug Development

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Target Identification and Validation in Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 986))

Abstract

The majority of human diseases, including cancer, are characterized by abnormal protein function. Proteins regulate virtually every cellular process and exhibit multiple kinds of post-translational modification that modulate expression levels and activation states, such as phosphorylation by protein kinases. Additionally proteins interact with each other in complex regulatory networks and signal transduction pathways modulated by feedback mechanisms. These pathways are disrupted in disease and altered by therapeutic drugs. Reverse phase protein microarray (RPMA) technology allows simultaneous measurement of numerous phosphorylated, glycosylated, cleaved, or total cellular proteins from complex mixtures in many samples at once. Therefore, RPMAs can provide a portrait of a cell’s signaling pathways in diseased states, before and after treatment with drugs, and allows comparison of changes in drug-resistant and sensitive cells. Furthermore, the technology offers a means of connecting genomic abnormalities in cancer to targetable alterations in protein signaling pathways, even for genetic events that seem otherwise undruggable. Consequently, the RPMA platform has great utility in many steps of drug development including target identification, validation of a pharmaceutical agent’s efficacy, understanding mechanisms of action, and discovery of biomarkers that predict or guide therapeutic response. RPMAs have become a powerful tool for drug development and are now being integrated into human clinical cancer trials, where they are being used to personalize therapy.

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Author information

Authors and Affiliations

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

    Maria Isabella Sereni, Mariaelena Pierobon & Emanuel F. Petricoin III

  2. Department of Obstetrics and Gynecology, University Campus Bio-Medico of Rome, Rome, Italy

    Maria Isabella Sereni, Mariaelena Pierobon & Roberto Angioli

  3. Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Mitchell J. Frederick

Authors
  1. Maria Isabella Sereni
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  2. Mariaelena Pierobon
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  3. Roberto Angioli
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  4. Emanuel F. Petricoin III
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  5. Mitchell J. Frederick
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Editor information

Editors and Affiliations

  1. Director, Department of Pharmacology, Boehringer Ingelheim RCV GmbH & Co KG, N/A, Vienna, N/A, Austria

    Jurgen Moll

  2. Project and Team Leader, Cell Biology, Nerviano Medical Sciences, Viale Pasteur 10, Nerviano, 20014, Milano, Italy

    Riccardo Colombo

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Sereni, M.I., Pierobon, M., Angioli, R., Petricoin, E.F., Frederick, M.J. (2013). Reverse Phase Protein Microarrays and Their Utility in Drug Development. In: Moll, J., Colombo, R. (eds) Target Identification and Validation in Drug Discovery. Methods in Molecular Biology, vol 986. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-311-4_13

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  • DOI: https://doi.org/10.1007/978-1-62703-311-4_13

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-310-7

  • Online ISBN: 978-1-62703-311-4

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