changes in squamous carcinoma - imedex,...
TRANSCRIPT
3/26/2012
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Genetic changes in squamous cell carcinoma
Martin Sos, M.D.Lung Cancer Group, Dept I of Internal Medicine, University of Cologne &
Max Planck Institute for Neurological Research, Thomas Lab
Advances in the treatment of lung cancer
9 99 9 9
5y s
urv
ival
rat
e %
1950
-195
9
1970
-197
9
1960
-196
9
1980
-198
9
1990
-199
9
Sun et al., Nat Rev Cancer. 2007Enzioni et al. 2003
70% are not operable
IV III I-IIStadium
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The era of genomic cancer therapy:towards personalized medicine
Ch E
Paradigm−shift:
Currently: Evaluation f ll Future
Sandler et al., NEJM (2006)
Chemo−Era: no progress for
20 years
shift: biologically
informed therapeutics
of genomically tailored medicine
Future
Schiller et al., NEJM (2002)
Shepherd et al., NEJM (2005)
Mok et al., ESMO LBA2 (2008)
No difference between different cytotoxics
2008:Bevacizumab andCetuximab are clinically
bli h d
2009:Proof of predictive
power of EGFR mutations
Adopted from M Scheffler; RK Thomas
2010:Proof of
principle ALK inhibition in
EML4−ALK fusion patients
Discovery of cancer signaling pathways enabled by the molecular biology revolution
OOrgan Tissue Cell
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Discovery of cancer signaling pathways enabled by the molecular biology revolution
Tissue Cell
Functionally interrogating cancer genome diversity bychemo genomics screening
Clinical trials
library
validationin‐vivo models
target validationComputational predictions
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600
700
n.n.ents
Molecular screening of lung cancer patients in real life
Screened patients 2011 = 1000
200
300
400
500
600 n.n.
mutated/ amplified / translocatedwt
ber
of lu
ng c
ance
r pa
tie
0
100
200
KRAS mut
BRAF mut
EGFR mut
FGFR1 amp
ALK fusion
PIKC3CA mut
Her2 amp
Her2 mut
num
b
Lukas Heukamp, Thomas Zander, Martin Sos, Marc Bos, Christian MattonetReinhard Büttner, Jürgen Wolf and network collaborators
ph I afatinib + panitumumab (T790Mpos ) 2012
Personalized trialsegfr
Overview adenocarcionoma in the LCGC network
ph I afatinib + panitumumab (T790Mpos.), 2012
ph I (FIM) BGJ 398, open
ph I (FIM) LDK 378, 04/11 / ph II,III crizotinib, open
ph I extension: sorafenib + everolimus, open
ph II AUY922 + trastuzumab, 2012
ph I: MEK162 + BEZ235, 2012
ph II vemurafenib, 2012
17.12
23.1752.36
kras
braf
pik3ca
alk
n.n.
ph II erlo + beva / FDG-, FLT-PET, DCE-MRI / open
ph I BIBF1120 + everolimus / DCE-MRI / open
Trials to identify imaging-based biomarkers
1.17
3.252.93
Lukas Heukamp, Thomas Zander, Martin Sos, Marc Bos, Christian MattonetReinhard Büttner, Jürgen Wolf and LCGC&network collaborators
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Clinical Lung Cancer Genome Project (PI: Roman
Thomas)
Goal: to develop a novel taxonomy of lung cancer
1. by analyzing chromosomal gene copy number2. by analyzing gene expression3. by analyzing oncogene mutation status4. by linking clinical outcome parameters to genomic lesionslesions
5. by performing centralized panel path review