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Clinical Proteomic Tumor Analysis Consortium(CPTAC)RFA RenewalsHenry Rodriguez, PhD, MS, MBADirector, Office of Cancer Clinical Proteomics Research,Division of Cancer Treatment and Diagnosis
CPTAC program current scopeGoalsAchieved throughDeepen our understanding of cancer (genotypeto-phenotype) by comprehensively characterizingtumors (proteomic and genomic molecular level),and to establish public resources (data, assays,images, reagents) for hypothesis-driven scienceTUMOR CHARACTERIZATION (2016-2021)Proteome Characterization Centers (PCCs) &Proteogenomic Data Analysis Centers (PGDACs)- treatment naïve tumor / nml adjacent, prospectiveTRANSLATIONAL RESEARCH (2017-2022)Support clinically relevant research projects thataddress mechanisms of treatment response,resistance, or toxicityProteogenomic Translational Research Centers (PTRCs) &Proteogenomic Data Analysis Centers (PGDACs)- pre-clinical and clinical trial samplesIntegrated research consortium that applies standardized comprehensive proteomicsand genomics workflows, strict biospecimen collection protocols (optimized forgenomics and proteomics) – ensuring rigor & reproducibility2
Tumor Characterization ProgramC P T A C(YR 4 of 5)ColonKidneyEndometrialOvarianLung adenoCell 2019Cell 2019Cell 2020Cell Rep Med 2020Cell 2020BreastGBM (pediatric)GBM (adult)Head & NeckCell 2020Cell 2020Cancer Cell 2020Cancer Cell 2020Lung SCCin progressPancreasin progressGBM (AYA)in progressI n t e r n a t i o n a lC o l l a b o r a t i o n sCPTACNIH ODOral squamousGastricLiverLung adenoNature Comm 2017Cancer Cell 2019Cell 2019Cell 20203
Translational Research Program(YR 3 of 5)CLINICAL TRIALSAMPLESPRE-CLINICAL RESEARCH;PILOT STUDIESAML Comprehensive proteogenomicsof AML cell lines with differentdriver mutations and subjectedto FDA-approved TKIs.Outcome: Proteomic profilesbased on driver mutations Piloted on 16 pts from BeatAMLtrial. Outcome: proteins andphosphoproteins associated withdrug sensitivity Expanding to large cohort (200pts from BeatAML trial) withsingle driver mutation (FLT3ITD). APPROVEDLeuk emia. 2018; PMID: 29743719Breast Developed micro-scale MStechnique for comprehensiveproteogenomics (breast PDXsingle-needle core biopsy) Piloted on 50 HER2 pt samplesfrom NSABP DP-1 trial.Outcome: HER2phosphorylation change foundbased on treatment outcome Expanding to 130 HER2 ptsamples from randomized phase3 trial. Application to NCTN trial.APPROVEDNat Commun. 2020; PMID: 31988290Ovarian Comprehensive proteogenomicsof intra-pt cell line pairs(pre/post-platinum resistance),refractory & sensitive PDX, and350 pt tumors (FFPE, FF, OCT).Outcome: Proteins associatedwith Pt resistance. Trained andvalidated on independent pttumors (FFPE and FF) Developing MS multiplex assay;Applying to NCTN randomizedphase 3 trial for samples. CLIA lab; PD markersBritish J of Cancer. 2018; PMID: 303858214
CPTAC Public Resources (data warehouse)Largest public repositories of proteogenomics datasets, assays, and reagentsProteomics DataTargeted Proteomic AssaysmAntibodies(Proteomic Data Commons)(CPTAC Assay Portal)(CPTAC Antibody Portal)620 TB total downloads2,553 assays753 mAbs(22 TB data available)(7,000 users/mth)(4,953 units sold)Proteomics DataAssaysAntibodiesGenomics DataImaging Data(Genomic Data Commons)(The Cancer Imaging Archive)591 TB total downloads(235 TB data available)Genomics Data5,675 images(2 TB downloads/mth)(1.5 TB data available)Imaging DataData PortalsAssay PortalAntibody Portal
What’s next for CPTACRecommendations: build on the achievements of CPTAC, while optimizing its scientific approachbased on Lessons Learned to accelerate molecularly oriented cancer research and clinical impactGoal 1: Comprehensive tumor characterizationGoal 2: Applying proteomics to clinical trial researchProteome Characterization Centers (PCCs) &Proteogenomic Data Analysis Centers (PGDACs)Proteogenomic Translational Research Centers (PTRCs) &Proteogenomic Data Analysis Centers (PGDACs) Extend CPTAC’s approach to 5 new cancer types Support clinically relevant research projects (pre-where questions remain on their proteogenomiccomplexityclinical in collaboration with clinical researchers anduse human biospecimens from clinical trials)Future directions (lessons learned):Future directions (lessons learned): Expand PTMs (beyond phospho, such as such as Extend the specialized analytical expertise andacetylation, ubiquitination, and glycosylation); addmetabolites (when appropriate); microenvironment;incorporate pre-clinical models, metastatic and rarecancers; retrospective samples (if possible) Host outreach activities of CPTAC’s resources andbioinformatics toolsinfrastructure to trial experts outside of the networkwith cancer interests beyond those selected byPTRCs Develop pilot studies (DCTD Steering Committee)that address needs in clinical trials brought forwardby the NCI6
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Proteome Characterization Centers (PCCs) & Proteogenomic Data Analysis Centers . Breast Cell 2020 Ovarian Cell Rep Med 2020 Oral squamous Nature Comm 2017 Liver Cell 2019 Lung adeno . Clinical Proteomic Tumor Analysis Consortium (CPTAC) Author: National Cancer Institute Subject: Clinical Proteomic Tumor Analysis Consortium (CPTAC)
