THIS COMPONENT IS ENTITITLED THE PROTEOMICS SHARED RESOURCE ABSTRACT Project Summary/Abstract The Siteman Cancer Center Proteomics Shared Resource (PSR) provides the enabling proteomics technology to accomplish the goals of the research programs of the SCC and its members. The SCC PSR offers in-depth proteomic analysis of biological fluids, cells and tumor tissue. The SCC PSR is one of the five lead Proteome Characterization Centers (PCC) for the NCI Clinical Proteomics Tumor Analysis Consortium, providing proteomics analyses of The Cancer Genome Atlas samples and the development of new biomarker assays for tumor tissues. The WU-PCC is supported by a U-24 grant from the NCI. The SCC PSR provides the proteomics expertise and analyses for Integrated Translational Genoproteomics Center at Washington University (ITGC) (David Mutch, PI). The WU-ITGC is supported by a U-10 mechanism from the NCI. An overarching objective of these NCI programs is to provide protein information at all levels of cancer research in accordance with the understanding that proteins are major effectors of the cancer phenotype. The ITGC at Washington University (ITGC) has been formed to support ongoing collaborations between the SCC PSR and the WU Genome Institute, and to complement the technical expertise of the TCGA and CPTAC programs with the accrual power and clinical expertise of the NRG Oncology cooperative group to provide clinical and biological annotation for the vast quantities of new data generated by genomics and proteomics platforms. To address the current technical challenges for the proteomic analysis of clinical samples such as tumor biopsy specimens, the expert staff members of the PSR develop and execute customized proteomic workflows that are adapted to standard operating procedures and integrated into clinical trial protocols. Quality controlled proteomics data sets are also generated for SCC members, individually and as part of the SCC Programs. The facilities include multiple, high-resolution mass spectrometric platforms that are equipped with automation for continuous operation. The PSR and the WU Genome Institute collaborate to build proteogenomic data analysis modules for basic and clinical cancer research. In this competitive renewal, we propose to develop new proteomic methods with a focus on the cancer kinome response to drug perturbations using high- precision, highly-multiplexed MS-based assays to underpin basic and clinical cancer research. Major challenges facing clinical proteomics are the limitations imposed by sample size (e.g. protein quantity), and tissue procurement protocols that minimize preanalytical variability and preserve labile post-translational modifications. We propose to address these challenges by a concerted effort within CPTAC, the WU-ITGC, and the SCC.