Keynote opening lecture at the grand opening of our new cyclotron facility, embedded in Radboud Translational Medicine and part of our Radboudumc Technology Centers. See http://www.radboudtranslationalmedicine.nl/nl/ for details.

1. Personalized Health(care):
more than just targeted medicines
Professor of Personalized Healthcare
Head Radboud Center for Proteomics, Glycomics
and Metabolomics
Coordinator Radboud Technology Centers
Senior Scientist Integrator Biomarkers
Prof Alain van Gool
Opening Radboud Translational Medicine
Nijmegen, 9 Dec 2015

2. My background in personalized health(care)
8 years academia (NL, UK)
(molecular mechanisms of disease)
13 years pharma (EU, USA, Asia)
(biomarkers, Omics)
4 years med school (NL)
(personalized healthcare, Omics, biomarkers)
4 years applied research institute (NL, EU)
(biomarkers, personalized health, nutrition)
1991-1996
(PhD)
1996-1998
(post-doc)
2009-2012
(visiting prof)
1999-2007 2007-2009 2009-2011
2011-now
2011-now (prof)
2 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
A person / citizen / family man
(adventures in EU, USA, Asia)

3. Source: Chakma, Journal of Young Investigators, 16, 2009
Principle of Personalized/Precision/Targeted Medicine
3
Molecular biomarkers as key drivers to select right patient for right drug
at right dose at right time: Companion Diagnostics
3 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

4. Example: Personalized Medicine in melanoma
Key biomarkers:
Stratification: BRAFV600E DNA mutation assay
Mechanism: P-ERK
Cyclin-D1
Efficacy: Ki-67
18FDG-PET, CT
Clinical endpoint: progression-free survival (%)
{Source: Flaherty et al, NEJM 2010}{Source: Chapman et al, NEJM 2011}
4 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

5. Companion diagnostics in current drug labels
Metabolism
Efficacy or
safety
{Source: www.fda.gov (June 2013)}
= molecular biomarker that indicates the right patient for right drug at
right dose at right time
5 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

6. Exponential developments in biomarker technologies
• Next generation sequencing
• DNA, RNA
• Risk analysis and therapy selection
• Mass spectrometry
• Proteins, metabolites
• Monitoring of disease and treatment effects
• Imaging
• Non invasive images, real time
• Spatial view of intact organs and organisms
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
6 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

7. Emerging companion diagnostics
Good examples personalized medicine in Oncology and Neurosciences:
• Cyp450, Her2/neu, BRCA, BRAF, EGFR, EML4/ALK, etc
Emerging companion diagnostics, also linked to non-drug therapies:
• Volker: Intestinal surgery → XIAP → Cord blood
• Beery twins: Cerebral palsy → SPR → Diet 5HTP
• Wartman: Leukemia → FLT3 → Sunitinib
• Gilbert: Healthy → BRCA → Mas/Ovarectomy
• Snyder: T2Diabetes → GCKR, KCNJ11 → Diet, exercise
• Lauerman: Scotoma, leg → JAK2 → Aspirin
• Bradfield: Healthy → CDH1 → Gastrectomy
Coming up: metabolic biomarkers, imaging biomarkers
7 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

8. Rational selection of best targets and biomarkers works
The 5R’s assessment:
• Right Target
• Right Tissue
• Right Safety
• Right Patients
• Right Commercial Potential
8 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

9. 9
Optimal Personalized / Precision / Targeted Medicine

10. People are more than linear pathways

11. People are more than linear pathways
{Source: Barabási 2007 NEJM 357; 4}
• People are different
• Different networks and influences
• Different risk factors
• Different preferences
11 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

12. Personalized health(care) in a systems view
12
12 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

13. Societal need in efficient personalized health(care)
{Source: prof Jan Kremer}
Towards cost effective care, less cure
13 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

14. Personal need in efficient personalized health(care)
It’s personal !
‘I want to stay healthy.’
‘If not, how do I get healthy?’
14 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

15. My route to Personalized Health(care)
15 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

16. Analogy: TOMTOM
GPS to a location
Amsterdam
Traffic jam
Amsterdam
Route 1 Route 2
= Default Traffic jam near Utrecht Alternative route
16 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

17. Personalized Health(care) model
GPS to health
Health
Route 1 Route 2
= Default
First signs of
disease risk
Alternative route
Now
Disease risk
Health
Now
Health
17 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

18. 18 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
18
New data
(generators, owners)

20. Key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
20 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

21. 1. What to measure?
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Gap 3
• Too much biomarker discovery
• Too little development to application
Alain van Gool, Workshop Neuroinformatics and personalized health care , Nijmegen, 26 Nov 201521
Biomarker innovation gaps!

22. Biomarker innovation gaps: some numbers
5 biomarkers/
working day
1 biomarker/
1-3 years
1 biomarker/
3-10 years
?
Eg Biomarkers in time: Prostate cancer
May 2011: n= 2,231 biomarkers
Nov 2012: n= 6,562 biomarkers
Oct 2013: n= 8,358 biomarkers
Nov 2014: n= 10,350 biomarkers
Oct 2015: n = 11,856 biomarkers
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Gap 3
Alain van Gool, Workshop Neuroinformatics and personalized health care , Nijmegen, 26 Nov 201522

23. 2. How much can it change?
Personalized
Intervention
of patients-like-me
Personal thresholds
of persons-like-me
Big
Biomarker
Data
Molecular
Non-molecular
Environment
…
HomeostasisAllostasisDisease
Time
Disease
Health
Selfmonitoring
Adapted from Jan van der Greef, TNO (2013)
Personal profile
Personalized health
Personalized medicine
Alain van Gool, Workshop Neuroinformatics and personalized health care , Nijmegen, 26 Nov 201523

24. 3. What should be the follow-up for me?
Personal profile data
Knowledge
Understanding
Decision
Action
24 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

25. Translation is key in Personalized Healthcare !
“I’m afraid you’re
suffering from an
increased IL-1β and
an aberrant miR843
expression”
Adapted from:
?
25 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

26. Shared decision making
Select personalized therapy
Treatment options
Successrates
Example from Prostate cancer patient guide
26 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
{Source: Peep Stalmeier}

27. Shared decision making
Treatment options
Pro’sCon’s
Select personalized therapy
Example from Prostate cancer patient guide
27 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
{Source: Peep Stalmeier}

28. Flipping the coin
Via the ónly constante in
healthcare: The patient
Via HC ICT systems
28 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
{Source: Lucien Engelen}

29. Patient
Radboud
Personalized Healthcare
A significant impact
on healthcare
Molecule
Population
29 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

30. Orientation across the spectrum
from molecule to man to population
Orientationacross
thespectrumofdiseases
Researcher
Research Theme
TechnologyCenter
Research support by Technology
30 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

31. www.radboudumc.nl/research/technologycenters
Genomics
Bioinformatics
Animal
studies
Stem
cells
Translational
neuroscience
Image-guided
treatment
Imaging
Microscopy
Biobank
Health
economics
Mass
Spectrometry
Radboudumc
Technology
Centers
Investigational
products
Clinical
studies
EHR-based
research
Statistics
Human
performance
Data
stewardship
Molecule
Flow
cytometry
31 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

32. About 250 dedicated people working in 18 Technology Centers, ~2000 users (internal, external), ~150 consortia
www.radboudumc.nl/research/technologycenters/
• Proteins
• Metabolites
• Drugs
• PK-PD
• Preclinical
• Clinical
• Behavioural
• Preclinical
• Animal facility
• Systematic review
• Cell analysis
• Sorting
• Pediatric
• Adult
• Phase 1, 2, 3, 4
• Vaccines
• Pharmaceutics
• Cyclotron
• Radio-isotopes
• Malaria parasites
• Management
• Analysis
• Sharing
• Cloud computing
• DNA
• RNA
• Internal
• External
• Early HTA
• Evidence-based
surgery
• Field lab
• Statistics
• Biological
• Structural
• Preclinical
• Clinical• Economic
viability
• Decision
analysis
• Experimental design
• Biostatistical advice
• Electronic Health Records
• Big Data
• Best practice
• In vivo
• Functional
diagnostics
• iPSC
• Organoids
32
• Cyclotron

33. Technology Center Investigational Products
www.radboudtranslationalmedicine.nl/
GMP licensed production of clinical grade
therapeutic materials
• Radio isotopes
• Cell therapies (cells, vaccins)
• Pharmaceutics
• Malaria parasites
33 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
{Source: Anne de Goede, Frans Pieters + team}

34. Technology Center Imaging
• State-of-the art (pre)clinical imaging equipment and expertise:
CT, MRI, US, PET/CT, SPECT/CT, photoacoustic imaging, fluorescence imaging
• Strongly linked to RTC Microscopy
• Covers spectrum from molecule to man to population
• Hardware, software, expertise, innovation, impact
34 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
{Source: Otto Boerman, Chris de Korte, David Norris, Sven Lafebre, Peter Friedl + team}

35. Technology Center Image-guided treatment
• Integrated workflow with imaging guidance in operation rooms
• Field lab environment to drive innovations
{Source: Jurgen Fütterer, Maroeska Rovers, Mathias Prokop + team}

36. Access
Combination of
• Science
• Technology
• Business
• Innovation
• Impact in health
www.radboudumc.nl/research/technologycenters/
(1H2015: 1.900 unique visitors, 26.000 page views)
36 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

37. Working together on the Radboud campus
(Spin-out)
companies
37 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

38. Radboud Research Facilities
• Shared facilities across Radboud campus, also made part of Gelderland facilities
• Initiated by funding 6.2M Eur Gelderland + 6.2M Eur Radboud University/ Radboudumc
www.ru.nl/radboudresearchfacilities/
38 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

39. Working with other networks
Region, nation, Europe, world
39 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

40. Takehome message
• Strategic focus on implementing Personalized Healthcare
• Strong technological and methodological infrastructure
• Continuous exploration of functional networks
40 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015

41. Acknowledgements
Ron Wevers
Jolein Gloerich
Hans Wessels
Dirk Lefeber
Monique Scherpenzeel
Leo Kluijtmans
Lucien Engelen
Nathalie Bovy
Paul Smits
Maroeska Rovers
Bas Bloem
the Technology Centers
and many others
www.radboudumc.nl/personalizedhealthcare
www.radboudresearchfacilities.nl
www.radboudumc.nl/research/technologycenters
alain.vangool@tno.nl
alain.vangool@radboudumc.nl
www.linkedIn.com
www.slideshare.net/alainvangool
Many collaborators
Jan van der Greef
Ben van Ommen
Bas Kremer
Lars Verschuren
Ivana Bobeldijk
Marjan van Erk
Carina de Jongh
Peter van Dijken
Peter Wielinga
Robert Kleemann
Suzan Wopereis
and many others And funders
CarTarDis
41 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015