U24CA271079

Proteogenomic Characterization of Tumor Tissues and Preclinical Models with High Precision - Summary

During the last 10 years of both CPTAC2 and CPTAC3, the JHU Proteome Characterization Center (JHU/PCC) has repeatedly demonstrated superior technological innovation and robust data generation that have played critical roles in the success of CPTAC's core mission. This mission involves accelerating the understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis technologies to different cancer types.

As one of the three current CPTAC3 PCCs, we have established robust and standardized proteomic analysis protocols and technologies. These have been applied to seven human cancer cohorts and an additional 200 patient-derived xenografts from the Patient-Derived Models Repository. Together with the Proteogenomic Data Analysis Centers (PGDACs), we have published articles on integrated proteogenomic studies in four cancer types.

For our CPTAC4 PCC application, our overarching goal is to generate accurate and reproducible data using sensitive, quantitative, and standardized technologies. We will leverage our established center's infrastructure and capitalize on our success in clinical cancer proteogenomic discoveries. This will allow us to characterize proteins, protein modifications, and protein complexes associated with genomic alterations of cancer from additional human tumor types and pre-clinical models.

We will identify unique features that are inherent to proteins, such as post-translational modifications covering acetylation and ubiquitination. Additionally, we will study protein-protein interactions, as well as glycosylation and phosphorylation, which have already been included in our current PCC.

We propose a three-step strategy to characterize defined sets of genomics-characterized samples using technology platforms validated during CPTAC3. The steps include: (1) discovery of target proteins from both clinical specimens and preclinical models using quantitative proteomics by tandem mass tags and data-dependent acquisition mass spectrometry; (2) verification of findings using orthogonal data-independent acquisition mass spectrometry; and (3) confirmation of the verified targets using high-throughput, CPTAC Tier 2 analytically-validated targeted multiple reaction monitoring mass spectrometry (MRM-MS) assays. We further propose pilot studies for technology improvement.

While this PCC application focuses on the proteomic characterization of clinical specimens and preclinical models, we believe that the understanding of and expertise in proteogenomic data analysis and translation will be critical for the success of the PCC and the overall CPTAC network.

We have assembled a team of outstanding investigators with complementary expertise and years of experience in the CPTAC program (CPTAC2 and CPTAC3). We also have evidence of successful collaborations with investigators/PIs from the CPTAC PGDACs and Proteogenomic Translational Research Centers (PTRCs).

We believe that our PCC offers the best opportunity for the successful characterization of biological and clinical specimens to discover and confirm cancer targets. This will ultimately advance precision cancer medicine.

The Johns Hopkins University

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]

Baltimore, Maryland 212051832 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 373% from $1,157,752 to $5,481,323.