Phosphoproteomic Assessment of Therapeutic Kinases for Personalized Therapy in Castration-Resistant Prostate Cancer
Technical Report,15 Sep 2015,14 Sep 2016
Rutgers, The State University of New Jersey New Brunswick United States
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Due to the overwhelming evidence for kinase activation in metastatic CRPC tissues, our objective is to utilize a targeted mass spectrometry MS approach for the evaluation of current druggable kinases in human prostate cancer biopsies that will ultimately guide personalized therapy decisions. We hypothesize that targeted MS can be effectively used for the stratification of prostate cancer patients based on detection of activated kinases in pre-clinical and biopsy tissues. We have begun to evaluate activated kinases using predesigned phosphopeptides via targeted MS. To date, we have evaluated 111 kinase phosphopeptide standards and were able to detect nearly 75 via targeted MS, nearly half of which at 400 attomole sensitivity. We are currently evaluating phosphopeptide enrichment methods to detect these phosphopeptide standards in small tissue lysate amounts equivalent to a biopsy in cell lines where known genetic alterations in kinases exist. Those experiments are ongoing prior to moving into clinical tissues.