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Molecular & Cellular Proteomics 4:346-355, 2005.
© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Use of Reverse Phase Protein Microarrays and Reference Standard Development for Molecular Network Analysis of Metastatic Ovarian Carcinoma^*

Katherine M. Sheehan^,, Valerie S. Calvert^¶, Elaine W. Kay, Yiling Lu^||, David Fishman^**, Virginia Espina, Joy Aquino^¶, Runa Speer, Robyn Araujo, Gordon B. Mills^||,, Lance A. Liotta, Emanuel F. Petricoin, III^¶, and Julia D. Wulfkuhle^,¶¶

From the United States Food and Drug Administration (FDA)-NCI Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, NCI, National Institutes of Health and the
^¶ FDA-NCI Clinical Proteomics Program, Office of Cell, Tissue and Gene Therapy, Center for Biologic Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland 20892, the
Department of Pathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Beaumont Road, Dublin 9, Ireland, the
^|| Department of Molecular Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77054, and the
^** National Ovarian Cancer Early Detection Program, New York University, New York, New York 10016

Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient’s metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.

^¶¶ To whom correspondence may be addressed: CBER/FDA, Bldg. 29A/2B20, HFM 710, 8800 Rockville Pike, Bethesda, MD 20892. Tel.: 301-402-0211; Fax: 301-827-0449; E-mail: wulfkuhlecber.fda.gov

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