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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
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)
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
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
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
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
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
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
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
Personalized health(care) in a systems view
12
12 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
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
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
My route to Personalized Health(care)
15 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
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
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 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
18
New data (generators, owners)
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
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 2015 21
Biomarker innovation gaps!
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 2015 22
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 …
Ho
meo
sta
sis
A
llo
sta
sis
D
isease
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 2015 23
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
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
Shared decision making
Select personalized therapy
Treatment options
Succ
ess
rate
s
Example from Prostate cancer patient guide
26 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
{Source: Peep Stalmeier}
Shared decision making
Treatment options
Pro’s
Con’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}
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}
Patient
Radboud Personalized Healthcare
A significant impact
on healthcare
Molecule
Population
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Orientation across the spectrum from molecule to man to population
Ori
enta
tio
n a
cro
ss
the
spec
tru
m o
f d
isea
ses
Researcher
Research Theme
Te
chn
olo
gy
C
ente
r
Research support by Technology
30 Alain van Gool, Opening Radboud Translational Medicine, Nijmegen, 9 Dec 2015
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
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
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}
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}
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}
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
Working together on the Radboud campus
(Spin-out) companies
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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
Working with other networks Region, nation, Europe, world
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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
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
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