Accession Number : ADA595692


Title :   Identification and Targeting of Tyrosine Kinase Activity in Prostate Cancer Initiation, Progression, and Metastasis


Descriptive Note : Annual summary rept. 30 Sep 2012-29 Sep 2013


Corporate Author : CALIFORNIA UNIV LOS ANGELES


Personal Author(s) : Drake, Justin ; Witte, Owen


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a595692.pdf


Report Date : Dec 2013


Pagination or Media Count : 86


Abstract : In metastatic castration resistant prostate cancer (CRPC) activation of kinase pathways may provide resistance to androgen withdrawal in the absence of activating mutations. To gain a better understanding of kinase activation patterns in metastatic CRPC, we utilized phosphotyrosine peptide enrichment and quantitative mass spectrometry to identify druggable targets in metastatic CRPC patients obtained at rapid autopsy. Evaluation of these rare metastatic CRPC samples for tyrosine phosphorylation and kinases revealed activated SRC, EGFR, RET, ALK, and MAPK1/3 and other targets. Importantly, these kinase activation patterns exhibited intrapatient similarity and interpatient heterogeneity implying clonal origins of these lesions. Phosphoproteomic analyses and identification of kinase activation states in metastatic CRPC patients have allowed for the prioritization of kinases for further clinical evaluation.


Descriptors :   *METASTASIS , *PHOSPHORUS TRANSFERASES , *PROSTATE CANCER , *RESISTANCE(BIOLOGY) , *TYROSINE , AUTOPSY , EXCISION , HETEROGENEITY , IDENTIFICATION , MASS SPECTROMETRY , MUTATIONS , PHOSPHORYLATION , SAMPLING


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE