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available"],"repository":["GPMDB"],"pubmed_abstract":["In prostate cancer, multiple metastases from the same patient share similar copy number, mutational status, erythroblast transformation specific (ETS) rearrangements, and methylation patterns supporting their clonal origins. Whether actionable targets such as tyrosine kinases are also similarly expressed and activated in anatomically distinct metastatic lesions of the same patient is not known. We evaluated active kinases using phosphotyrosine peptide enrichment and quantitative mass spectrometry to identify druggable targets in metastatic castration-resistant prostate cancer obtained at rapid autopsy. We identified distinct phosphopeptide patterns in metastatic tissues compared with treatment-naive primary prostate tissue and prostate cancer cell line-derived xenografts. Evaluation of metastatic castration-resistant prostate cancer samples for tyrosine phosphorylation and upstream kinase targets revealed SRC, epidermal growth factor receptor (EGFR), rearranged during transfection (RET), anaplastic lymphoma kinase (ALK), and MAPK1/3 and other activities while exhibiting intrapatient similarity and interpatient heterogeneity. Phosphoproteomic analyses and identification of kinase activation states in metastatic castration-resistant prostate cancer patients have allowed for the prioritization of kinases for further clinical evaluation."],"pubmed_title":["Metastatic castration-resistant prostate cancer reveals intrapatient similarity and interpatient heterogeneity of therapeutic kinase targets."],"pubmed_authors":["Drake Justin M JM,Graham Nicholas A NA,Lee John K JK,Stoyanova Tanya T,Faltermeier Claire M CM,Sud Sudha S,Titz Björn B,Huang Jiaoti J,Pienta Kenneth J KJ,Graeber Thomas G TG,Witte Owen N ON,","Drake Justin M JM, Graham Nicholas A NA, Lee John K JK, Stoyanova Tanya T, Faltermeier Claire M CM, Sud Sudha S, Titz Björn B, Huang Jiaoti J, Pienta Kenneth J KJ, Graeber Thomas G TG, Witte Owen N ON"],"name_synonyms":["Transphosphorylases, Castrations, Adenocarcinoma of the Prostate, insensitive, resistant, PROSTATIC NEOPL, Prostate Neoplasms, Kinases, Adenocarcinoma of prostate (disorder), Neoplasms, ATP., Prostatic Neoplasms, \"malignant tumor of prostate (disorder)\" EXACT [SNOMEDCT_2005_07_31:399068003], Cancers, NEOPL PROSTATIC, Phosphotransferases, Prostate Neoplasm, NEOPL PROSTATE, Carcinoma of Prostate, metastatic, Prostatic Neoplasm, \"prostatic cancer\" EXACT [CSP2005:2016-2641], Cancer of the Prostate, Prostatic Cancer, heterogeneity, Neoplasm, Prostatic Cancers, Prostatic, PC, Kinase, PROSTATE NEOPL, adenocarcinoma of prostate, ATP Phosphotransferases, \"malignant tumor of the prostate\" EXACT [NCI2004_11_17:C7378], Cancer of Prostate, Prostate Cancer, Carcinoma of the Prostate, Prostate, Gonadectomies, Gonadectomy, Cancer, \"malignant tumor of prostate (disorder)\" EXACT [SNOMEDCT_2005_07_31:363448003], Prostate Cancers"],"description_synonyms":["activated cell autonomous cell death, insensitive, PROSTATIC NEOPL, Prostate Neoplasms, Heterograft, Adenocarcinoma of prostate (disorder), Neoplasms, prostate gland cancer cell line, AUTSX5, number, \"malignant tumor of prostate (disorder)\" EXACT [SNOMEDCT_2005_07_31:399068003], CaP cell line, Spectrum Analyses, NEOPL PROSTATIC, TRANSPL HETEROL, CCN3, Transplantations, QM, presence, NEOPL PROSTATE, peptide, heterologous transplantation., MOD_RES Phosphotyrosine, Mass, Prostatic Cancers, Analysis, Cancer of Prostate, Carcinoma of the Prostate, Mass Spectroscopy, Gonadectomies, Prostate Cancers, Mass Spectrum Analysis, treatment, portion of tissue, Postmortem Examination, Adenocarcinoma of the Prostate, Post-Mortem Examinations, Analyses, Prostatic Neoplasms, Tissue, Heterografts, IGFBP9, activated T-lymphocyte autonomous cell death, Examination, IBP-9, PCa cell, Prostatic Neoplasm, activated T cell apoptosis, Cancer of the Prostate, Xenotransplantations, L10, disease management, Prostatic, NOVh, Postmortem Examinations, adenocarcinoma of prostate, Post-Mortem Examination, \"malignant tumor of the prostate\" EXACT [NCI2004_11_17:C7378], Heterologous, activated T-cell autonomous cell death, Cancer, data, Prostates, Phosphotyrosine, CaP cell, DXS648, Entire prostate, Spectrum Analysis, Post-Mortem, activated T lymphocyte autonomous cell death, Spectroscopy, polypeptide, count in organism, Postmortem, XENOTRANSPL, count, IGFBP-9, Tyrosine O phosphate, male prostate, Examinations, Prostatic Cancer, Neoplasm, tissue portion, NOV, simple tissue, PlexA1, Heterologous Transplantations, Mass Spectrum Analyses, Gonadectomy, Mass Spectrum, Xenograft, Castrations, Plxn1, Xenotransplantation, resistant, distinct, Transplantation, Spectrometry, PCa cell line, HETEROL TRANSPL, Cancers, Xenografts, ACAD, mKIAA4053, Prostate Neoplasm, prostate tumor cell line, Carcinoma of Prostate, Autopsies, metastatic, \"prostatic cancer\" EXACT [CSP2005:2016-2641], prostate carcinoma cell line, C130088N23Rik, dihydrogen phosphate (ester), Tyrosine-O-phosphate, 2600013D04Rik, PC, quantitative, Post Mortem Examination, DXS648E, PROSTATE NEOPL, L-tyrosine, Prostate Cancer, prostate, Prostate, prostata, presence or absence in organism, \"malignant tumor of prostate (disorder)\" EXACT [SNOMEDCT_2005_07_31:363448003]"],"pubmed_title_synonyms":["Transphosphorylases, Castrations, Adenocarcinoma of the Prostate, insensitive, resistant, PROSTATIC NEOPL, Prostate Neoplasms, Kinases, Adenocarcinoma of prostate (disorder), Neoplasms, ATP., Prostatic Neoplasms, \"malignant tumor of prostate (disorder)\" EXACT [SNOMEDCT_2005_07_31:399068003], Cancers, NEOPL PROSTATIC, Phosphotransferases, Prostate Neoplasm, NEOPL PROSTATE, Carcinoma of Prostate, metastatic, Prostatic Neoplasm, \"prostatic cancer\" EXACT [CSP2005:2016-2641], Cancer of the Prostate, Prostatic Cancer, heterogeneity, Neoplasm, Prostatic Cancers, Prostatic, PC, Kinase, PROSTATE NEOPL, adenocarcinoma of prostate, ATP Phosphotransferases, \"malignant tumor of the prostate\" EXACT [NCI2004_11_17:C7378], Cancer of Prostate, Prostate Cancer, Carcinoma of the Prostate, Prostate, Gonadectomies, Gonadectomy, Cancer, \"malignant tumor of prostate (disorder)\" EXACT [SNOMEDCT_2005_07_31:363448003], Prostate Cancers"],"pubmed_abstract_synonyms":["para Tyrosine, insensitive, Heterograft, MTC1, CaP cell line, p42mapk, Errb1, ALK tyrosine kinase receptor, NEOPL PROSTATIC, TRANSPL HETEROL, phosphorylation, PIG61, peptide, rat, anaplastic lymphoma kinase, AI552599, Kinase, Analysis, Carcinoma of the Prostate, Gonadectomies, Mass Spectrum Analysis, treatment, portion of tissue, Adenocarcinoma of the Prostate, Post-Mortem Examinations, Analyses, Identification, 2-amino-3-(4-hydroxyphenyl)propanoic acid, 3-(p-Hydroxyphenyl)alanine, Tissue, number of, Prostatic Neoplasm, ASV, Cancer of the Prostate, Xenotransplantations, Tyr, disease management, 9030024J15Rik, ALK tyrosine kinase receptor precursor protein, Postmortem Examinations, Post-Mortem Examination, ATP Phosphotransferases, \"malignant tumor of the prostate\" EXACT [NCI2004_11_17:C7378], RET51, Transfections, ATP, NISBD2, MNK1, Prostates, Wa5, CaP cell, 2-Amino-3-(p-hydroxyphenyl)propionic acid, mouse, ERK-2, ERK1, ERK2, Erk2, extra or missing physical or functional parts, para-Tyrosine, Entire prostate, Spectrum Analysis, Post-Mortem, Tyrosine, Spectroscopy, CDHR16, transfect, Postmortem, p41mapk, count, wa2, HSCR1, Tyrosine O phosphate, tissue portion, simple tissue, Heterologous Transplantations, activation, Tcrz protein, PTC, Xenograft, Transphosphorylases, Xenotransplantation, resistant, Transplantation, SRC1, EGFR, L-isomer, Spectrometry, c-SRC, p38, Identifications (Psychology), PCa cell line, Xenografts, MEN2A, MEN2B, human, L isomer, C78273, Carcinoma of Prostate, Autopsies, metastatic, Patient, CD246 antigen, p41, p40, dihydrogen phosphate (ester), p44, Tyrosine-O-phosphate, L-Tyrosine, L-tyrosine, prostate, Prostate, prostata, 9030612K14Rik, \"malignant tumor of prostate (disorder)\" EXACT [SNOMEDCT_2005_07_31:363448003], p44erk1, receptor tyrosine-protein kinase erbB-1, NBLST3, PROSTATIC NEOPL, proto-oncogene c-ErbB-1, Prostate Neoplasms, Adenocarcinoma of prostate (disorder), Neoplasms, prostate gland cancer cell line, number, \"malignant tumor of prostate (disorder)\" EXACT [SNOMEDCT_2005_07_31:399068003], Spectrum Analyses, mENA, Transplantations, presence, NEOPL PROSTATE, heterologous transplantation, RET-ELE1, AA407128, Client., normoblast, MOD_RES Phosphotyrosine, anaplastic lymphoma receptor tyrosine kinase, Prostatic Cancers, Mass, Tcrz, Prkm1, EGF receptor activity, Prkm3, p42-MAPK, p60-Src, anaplastic lymphoma kinase Ki-1, Cancer of Prostate, Mass Spectroscopy, Prostate Cancers, ERK, PRKM1, PRKM2, Postmortem Examination, ALK protein, Prostatic Neoplasms, Heterografts, Anaplastic lymphoma kinase, Examination, PCa cell, Erk-1, 2.7.10.1, L Tyrosine, Clients, has or lacks parts of type, heterogeneity, Prostatic, Tyrosin, pp60c-src, adenocarcinoma of prostate, Methylations, Heterologous, Cancer, Alk protein, Phosphotyrosine, Esrk1, TGF-alpha receptor activity, ERBB, Phosphorylations, Phosphotransferases, c-Ret, mereological quality, polypeptide, count in organism, XENOTRANSPL, epidermal growth factor receptor activity, tirosina, male prostate, CD246 protein, Examinations, Prostatic Cancer, Neoplasm, CDHF12, methylation, Mass Spectrum Analyses, Gonadectomy, Mass Spectrum, Castrations, distinct, Kinases, P42MAPK, AW259666, HETEROL TRANSPL, patient, ERBB1, Cancers, C9H11NO3, wa-2, MAPK2, MAPK1, Prostate Neoplasm, prostate tumor cell line, AU018647, \"prostatic cancer\" EXACT [CSP2005:2016-2641], prostate carcinoma cell line, Errp, ERT1, ERT2, Erbb, cardinality, PC, transforming growth factor-alpha receptor activity, quantitative, Post Mortem Examination, PROSTATE NEOPL, Prostate Cancer, p44mapk, CD246, HER1, RET9, presence or absence in 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File: Batch3_RA14LiverMetr2-35.mzml. Published as part of Proc Natl Acad Sci U S A. 2013 Nov 18  . From the Abstract: {{i}} ... We evaluated active kinases using phosphotyrosine peptide enrichment and quantitative mass spectrometry to identify druggable targets in metastatic castration-resistant prostate cancer obtained at rapid autopsy. We identified distinct phosphopeptide patterns in metastatic tissues compared with treatment-naive primary prostate tissue and prostate cancer cell line-derived xenografts ... {{/i}}","dates":{"submission":"2013-11-21"},"accession":"GPM11210023535","cross_references":{"pubmed":["24248375"],"Pride":["PXD000238"],"pride":[],"Pride Archive":["PXD000238"]}}