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.

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. 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. 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. 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. 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. 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. 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. 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. 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. Strengthen NCT Partnerships
German Consortium for Translational Cancer Research (DKTK)
Fusing
High-Throughput Technologies
with
Hypothesis-driven,
Stratification & Intervention
towards
Personalized Medicine

11. NATIONAL CENTER FOR
TUMOR DISEASES
NCT HEIDELBERG