U24CA270823

Center of Excellence for High Throughput Proteogenomic Characterization - Project Summary

Cancer proteogenomics encompasses methods that integrate mass spectrometry (MS)-based measurements of protein abundance and post-translational modifications (PTMs) with genomic, epigenomic, and transcriptomic data from preclinical cancer models and tumor samples.

The multidisciplinary Proteogenomic Characterization Center we propose will employ a range of state-of-the-art MS-based proteomic and metabolomic technologies to systematically generate and integrate high-quality, comprehensive, and quantitative proteomic and metabolomic data with genomic data.

Our overarching goals are to leverage the integrated data to identify signatures of cancer drivers, detect signaling network adaptations, and provide information on PTMs that affect cellular signaling, molecular complex formation, and protein location, translation, and stability in human biospecimens and relevant models of cancer.

Peptidomes of the Class I and II human leukocyte antigens (HLA) of the tumors will also be analyzed to shed light on tumor-immune escape mechanisms and antigen processing in cancer, improve algorithms for prediction of antigen display and immunogenicity, and inform the development of personalized cancer vaccines.

We hypothesize that integrating deep, high-quality, quantitative proteomic and, especially, PTM-omic, HLA-peptidomic, and metabolomic data with genomic and transcriptomic data will provide novel insights into the pathophysiology of cancer and help to identify new, actionable targets for drug development and treatment.

Data will be rapidly distributed to the cancer biology and clinical communities, as we have done for the past 15 years in the NCI-CPTAC program. The resulting datasets will enable a broad range of investigation by many teams, accelerating molecularly-oriented cancer research toward biological and clinical impact.

We will also systematically develop and apply high sensitivity targeted MS assays to peptide/protein targets identified in the discovery arm, with an emphasis on posttranslationally-modified peptides in signaling cascades, oncogenic pathway regulators and effectors, and druggable proteins. Assays will use stable isotope-labeled standards for unambiguous identification and quantification and follow Tier 2 guidelines developed from the community-based effort led by the Broad Proteomics Team.

Existing technologies will be further developed and automated to enable comprehensive analysis of rare tumor cell populations, to evaluate tumor heterogeneity, to increase depth and breadth of post-translational modification analysis, and to improve depth, reliability, and repeatability of peptide identification and quantification in general by intelligent data acquisition.

The Broad Institute

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Cambridge, Massachusetts 021421027 United States

Single Zip Code

Proteome Characterization Centers (PCCs) for Clinical Proteomic Tumor Analysis Consortium (U24 Clinical Trial Not Allowed) (RFA-CA-21-023)

Amendment Since initial award the total obligations have increased 292% from $1,088,100 to $4,262,276.