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Festival of Genomics 2016 London: Real-time Exploration of the Cancer Genome, the Human Immune System (REHIS) and other NCT projects

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This presentation covers the NCT presentation of the 2016 Festival of Genomics workshop "Big Medical Data in Precision Medicine: Challenges or Opportunities?" on Jan 19, 2016 in London.

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Festival of Genomics 2016 London: Real-time Exploration of the Cancer Genome, the Human Immune System (REHIS) and other NCT projects

  1. 1. NATIONAL CENTER FOR TUMOR DISEASES NCT HEIDELBERG Precision Oncology at NCT The Paradigm Shift: Imaging each Individual Patient‘s Cancer At the Molecular Level
  2. 2. NCT Precision Oncology Program NCT OMICS CLINICAL EVALUATION & TRIALS TARGET EXPLOITATION TARGET CHARACTERIZATION TARGET IDENTIFICATION PATIENT ADMISSION – DOCUMENTATION - BANKING DATA INTEGRATION Organized in SAP HANA STRATIFIED ONCOLOGY EARLY DIAGNOSIS RISK STRATIFICATION PREVENTION NCT DataThereHouse INDIVIDUALIZED THERAPY MOLECULAR TUMOR BOARD DIAGNOSIS & SAMPLING INDIVIDUALIZED THERAPY & TRIALS NCT OMICS PATIENT ADMISSION ENROLLMENT CLINICAL DATA RESPONSE RESISTANCE PREVENTION BIOINFORMATICS CLINICAL REPORT NCTDataThereHouse(SAPHANA) NCT MASTER Workflow
  3. 3. National High Throughput Sequencing Core Unit ICGC INFORM NCT Molecular Diagnostics Program 2009 2010 2011 2012 Illumina xten Cluster ICGC Sequencing NCT Precision Oncology Program 2015 Mutation in RNAseq? Mutation in RNAseq? Alternative Splicing Alternative Splicing fastq QCfastq QC alignmentalignment lane merging lane merging duplicatesduplicates genotype matching genotype matching calculate coverage calculate coverage OneTouchPipeline PRIMARY ANALYSIS SNVsSNVs Mutation annotation Mutation annotation INDELsINDELs Copy number variants Copy number variants Pathogen integration Pathogen integration Ploidy prediction Ploidy prediction Structural Variants Structural Variants SECONDARY ANALYSIS RNA sequences RNA sequences DNA sequences DNA sequences TERTIARY ANALYSIS: „INTERPRETATION“ NCT Applied Bioinformatics
  4. 4. Molecular Tumor Board* Validation Clinical Evaluation Bioinformatic Analysis Sequencing Patient Sample Asservation PI3K-AKT- mTOR BasketTrialwithPathwayPrograms RAF-MEK- ERK Tyrosine Kinases Developmental Pathways Unbiased Functional Testing Focused Functional Testing Feed Back Results Adapt Treatment/ Functional Testing DDR Signaling Stefan Fröhling, Christoph Heining, Hanno Glimm, Stefan Gröschel Claudia Scholl (Functional Genomics) DKTK – LMU München, Frankfurt, Dresden, Essen/Düsseldorf, Freiburg, Berlin Other NCT MASTER – Registry & Interventional Trial Hypermutated/ ImmunoTherapy NCT MASTER Current Status NCT MASTER – Registry & Interventional Trial
  5. 5. INFORM = INdividualized therapy FOr Relapsed Malignancies in childhood Angelika Eggert, Stefan Pfister, Olaf Witt, Peter Lichter & Study Groups of the GPOH EXCEL ALL AML HGG (incl. DIPG) Medullo/Ependym. Ewing Sarcoma Neuroblastoma NHL Osteosarcoma Phase I/II Rhabdomyosarcoma Rhabdoid Tumors Enrollment Standard of Care: Backbone Chemotherapy Backbone Targeted Drug 1 Targeted Drug 2 Feasibility-Registry Study (Year 1+2) Clinical Trial (Year 3-5) INNOVATION Development of experimental systems for functional validation Cancer cell lines Immortalized non- transformed cell lines Isogenic cell lines Introduction/modification of genetic alterations by lentiviral gene or shRNA transfer or CRISPR/Cas9 technology InvitroInvivo Functional annotation of molecular lesions • Viability/proliferation • Apoptosis/cell cycle • Anchorage independence • Invasion/migration • Pathway activation • Others • Tumorigenicity (mouse, CAM) 1 • Genome-wide or targeted shRNA screens • Genome-wide or targeted CRISPR/Cas9 screens Unbiased identification of functional dependencies2 Invitro In collaboration with Claudia Scholl, Michael Boutros (NCT Heidelberg/DKFZ), and Frank Buchholz (NCT Dresden) Functional Genomics
  6. 6. Genomics of Drug Sensitivity of Primary Cancer Cells Parallel molecular and functional characterization Zenz et al. NCT Immunotherapy Program Medical Oncology Jäger Neurooncology Platten/Wick Immunogenetics Krammer Mol. Oncology of Gastrointestinal Tumors Rienk Offringa Translational Immunology Beckhove Applied Tumor Immunity Halama/Jäger Recombinant Therapeutic Antibodies Krauss/Arndt Immunology of Malignant Melanoma Enk / Hassel Cellular Immunology Rodewald Innate Immunity Cerwenka Beckhove J Clin Invest 2009 & 2010 Krammer Blood 2006 Hämmerling Nature 2008 Cerwenka Blood 2008 Jäger PNAS 2010 MISSION • Use the patients immune system for treating the tumor • Reinduce immunosurveillance FOCUS • Shape host-tumor-interactions at different levels: - Checkpoint blockade - Modulation of local environment - Antibody based therapy - T cell-based therapy (vaccine/adoptive transfer) - Genetically modified T cell therapy (TCRs/CARs) - Develop novel reagents/strategies into clinical application NETWORK • Cancer Immunotherapy Consortium CRI/Ludwig New York • CIMT/CRI/AACR • DKTK • Spitzencluster für individualisierte Immunintervention CI3 • Alliances Roche/Genentech, Bayer
  7. 7. NCT Radiation Oncology Program Heidelberg Ion Therapy (HIT) 3 Clinical Rooms, 1 Experimental Room Synchrotron 400 MeV/u, Active Scanning, Ion Gantry (600 t) Particles: Clinical: H, C-12 Experimental: O-14, He-4 Radiation Oncology Debus Translational Radio- Oncology Abdollahi Medical Physics in Radiation Therapy Jäckel Medical Physics in Radiology Ladd Radiology Schlemmer (Delorme), Kauczor NuclearMedicine Haberkorn Radiopharmacy Kopka Mol. Radiation Oncology Huber ParticleTherapy Herfarth NCT Cancer Prevention, Early Detection and Outcomes Program Departments Preventive Oncology Brenner (temporary) Division of Clinical Epidemiology and Aging Research. Brenner Molecular Genetic Epidemiology Hemminki Cancer Epidemiology Kaaks Epigenomics and Cancer Risk Plass Cancer Early Detection Von Knebel-Doeberitz Tobacco Control Pötschke-Langer Psychooncology Herzog MISSION To reduce the burden of cancer through • Reduction of risk factors (primary prevention) • Early detection and screening (secondary prevention) • Improving outcomes and quality of life of cancer patients (tertiary prevention) FOCUS • Identification of genetic, behavioral and environmental risk factors and avenues for prevention with novel methods and technologies • Population-wide and risk-adapted (personalized) early detection and screening programs • Cancer outcomes research • Clinical trials: early detection, behavioral interventions NETWORKS • Leadership in national & international consortia: e.g. IMPACT Consortium, DKTK, National Cohort Selected Publications Lancet 2014 BMJ 2014 Science 2013 JCO 2011,2012,2014 JAMA 2010
  8. 8. Display Data from Various Sources for a Comprehensive Overview of Information Relevant for Personalized Treatment NCT NCT DataThereHouse INDIVIDUALIZED TREATMENT PLAN SEQUENCING DATA ARRAY DATA CLINICAL PATHWAYS UNSTRUCTURED DATA DOCOTOR’S LETTER STRUCTURED DATA PHYSICIAN SCIENTIST TUMOR BOARD CASE MANAGER STUDY NURSE DOCUMENTALIST ARZT FORSCHERCASE MANAGER REPORTER DOKUMENTAR PHYSICIAN SCIENTIST = NEUE STUDIE EINSCHLUSS & AUSSCHLUSS KRITERIEN BOARD SPRECHSTUNDE/ AMBULANZ SOP* BEGLEITENDE DIENSTE KIS, PACS, REGISTER KIS, PUBMED, UPTODATE, BIOBANK, INTRANET, REGISTER PATIENT HYPOTHESE STUDIEN PROTOKOLL AUFKLÄRUN/ SCREENING STUDY NURSE REPORT EINBINDUNG THERAPIE AM NCT ODER EXTERN LOI* THERAPIE POP* ARZTBRIEF PATIENTENAKTE ABLAUF DATENFLUSS PATIENTENPFAD DATENBANK ARTEFAKTE KONFERENZ BEGLEITENDE DIENSTE Current Scenario NCT NCT DataThereHouse
  9. 9. NCT Clinical Development Strategy PATIENT THERAPIE AM NCT KLINISCHE STUDIEN DIAGNOSE KLINISCHES KREBSREGISTER NCT IS-H, PUBMED, UPTODATE, BIOBANK, INTRANET, IS-H, PACS MONITORING DOKUMENTAR ARZT FORSCHER PUBLIKATION IS-H, PUBMED, UPTODATE, BIOBANK, INTRANET, IS-H, PACS FORSCHER ARZT DOKUMENTAR Organized in SAP HANA DOKUMENTAR DOKUMENTAR NCT DataThereHouse NCT CANCER REGISTRY NCT Partnerships Academic Collaboration DKTK EMBL DKFZ-ZMBH ALLIANCE Joint Industry-Academia Collaboration Cancer Core Europe Consortium Centers
  10. 10. Strengthen NCT Partnerships German Consortium for Translational Cancer Research (DKTK) Fusing High-Throughput Technologies with Hypothesis-driven, Stratification & Intervention towards Personalized Medicine
  11. 11. NATIONAL CENTER FOR TUMOR DISEASES NCT HEIDELBERG

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