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Identification of diagnostic and therapeutic targets of pancreatic cancer using proteomic approaches

Pancreatic cancer remains one of the most lethal of all the solid malignancies. Using a quantitative proteomic strategy, we have carried out profiling studies to identify novel biomarkers and therapeutic targets in pancreatic cancer. Phosphotyrosine profiling revealed aberrant activation of epidermal growth factor receptor (EGFR) in a subset of pancreatic cancers. This correlated with phospho‐EGFR staining and response to the EGFR inhibitor, erlotinib, in mice carrying pancreatic cancer xenografts demonstrating the utility of activated EGFR as a biomarker that could be used to guide therapeutic decisions. Proteomic profiling of membrane fractions identified several proteins that are differentially expressed in pancreatic cancers. Immunohistochemical validation of one of the candidate markers, myeloid associated differentiation marker (MYADM), confirmed overexpression of this molecule in greater than 80% of pancreatic adenocarcinomas. Our studies emphasize the utility of advanced proteomic approaches in identifying novel biomarkers and therapeutic targets.