Identification and Targeting of Tyrosine Kinase Activity in Prostate Cancer Initiation, Progression, and Metastasis
Abstract
In metastatic castration resistant prostate cancer (CRPC) activation of kinase pathways mayprovide resistance to androgen withdrawal in the absence of activating mutations. To gain abetter understanding of kinase activation patterns in metastatic CRPC, we utilized phosphotyrosinepeptide enrichment and quantitative mass spectrometry to identify druggable targetsin metastatic CRPC patients obtained at rapid autopsy. Evaluation of these rare metastaticCRPC samples for tyrosine phosphorylation and kinases revealed activated SRC, EGFR, RET, ALK,and MAPK1/3 and other targets. Importantly, these kinase activation patterns exhibitedintrapatient similarity and interpatient heterogeneity implying clonal origins of theselesions. Phosphoproteomic analyses and identification of kinase activation states inmetastatic CRPC patients have allowed for the prioritization of kinases for further clinicalevaluation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2014
- Accession Number
- AD1106932
Entities
People
- Justin M Drake
- Owen N Witte
Organizations
- University of California