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A more recent version of this article appeared on April 1, 2005.
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Submitted on January 13, 2005
Revised on January 24, 2005
Accepted on January 25, 2005

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 Liu, David S. Fishman, Virginia Espina, Joy Aquino, Runa Speer, Robyn Araujo, Gordon B. Mills, Lance A. Liotta, Emanuel F. Petricoin, and Julia D. Wulfkuhle

Office of Cell, Tissue and Gene Therapies, CBER/ FDA, Bethesda, MD 20892

Corresponding Author: petricoin{at}cber.fda.gov

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, a critical question is 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 endpoints 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 cocktail of phosphorylated peptides to begin to address this challenge.


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