Post on 05-Jun-2018
Toni K. Choueiri, MD
Director and Disease Center Leader
The Lank Center for Genitourinary Oncology
President of Medical Staff
Dana-Farber Cancer Institute
The Jerome and Nancy Kohlberg Endowed Chair
Harvard Medical School
Boston, Massachusetts
@DrChoueiri
Eugene P. Schonfeld Lecture
“my RCC and non-RCC life path”
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The Eternal Magic of BeirutFor many of us, it’s synonymous with war and strife. But for the
artists, chefs, designers, architects and scholars who live
there, Beirut will always be a place where ideas and beauty
flourished ... and flourish still.
By MICHAEL SPECTER, MAY 2, 2016
Beirut: The Middle East's party capitalBy Tim Hume, CNN
Updated 7:40 AM ET, Fri August 10, 2012
Not clear first going into GU or Kidney cancer
• Papers in:
– Benign Hematology (Lichtin, 1 )
– Breast Cancer (Budd, 4)
– Multiple Myeloma (Hussein, 5)
– Thrombosis in Cancer patients
(Deitcher, 2)
– Hodgkin lymphoma (Bolwell, 1)
– Skin (Olencki 1)
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Early Years (2003)
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• Also @Cleveland Clinic: 2003-2007:
•Derek Raghavan (Cancer Center Director)
•Rob Dreicer
•Eric Klein, Andy Novick (Urology)
•Tim Gilligan
•Jorge Garcia
•Brian Rini
•Ming Zhou (Pathology)
•Laura Wood, RN
•Brian Bolwell, Mikkael Sekeres (Heme)
•Paul Elson (Stats)
•Many co-fellows
COMPARZ Trial (2013)
Bernard Escudier and the French Connection (2003-
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2015 ESMO Presidential session 2016 ESMO Presidential session
Danny Heng: yes he believes In prognostication (psychic)
and no, he is not Irish (IMDC database Consortium)
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Calgary: Why he's a 2015 Top 40 under 40
International mRCC Database Consortium
Tissue Clinical Data
IMDC Biobank Repository
for Translational Research
(IMDC-BTR)
25+ Institutions, 10 countries
Biomarker Discovery + Validation
Tissue Microarrays
Primary and metastatic analyses
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-47k employees
-22k students
-6500 job openings/year
-If LMA was a State=7th in NIH
funding
(LMA)
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The Longwood Area
Across the River: MGH, MIT,
Broad Institute, Harvard University,
Biotech (Novartis, Merck, Pfizer,
AZ, Abbott…)
David McDermottBIDMC
Toni ChoueiriDFCI Othon IliopoulosMGHBill KaelinDFCI Dror MichaelsonMGH
Sabina SignorettiBWH
Kidney Cancer Program at Dana-Farber/Harvard Cancer Center
Study Drug Target Phase Status
Dalantercept ALK1 II Recruiting
X4P-001 CXCR-4 I Recruiting
Cabozantinib VEGF III Completed / Positive
Cabozantinib MET/Axl II Completed / Positive
PT-2385 HIF-2 I Recruiting
Discovery ImpactTranslation
And Mike Atkins who
started most this…
Kidney SPORE Co-leader
DF/HCC Kidney Cancer Program
Leader
-SELECT Trial
-Cytokine Working group
-Early trials with Nivolumab and
Atezolizumab.
And many more….
David McDermott, MD
Harvard Urology SPORE Retreat @MGH, 2016
DFCI/MGH/BIDMC
Yale Cancer Center
MSKCC
MD Anderson
ASCO CDA
Bill Kaelin, MET and Cabozantinib, the real story...
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Sometime in 2009….
786-O VHL -/- cells with shRNA against MET
Median OS
mo (95% CI)
Cabozantinib (N=330) 21.4 (18.7-NE)
Everolimus (N=328) 16.5 (14.7-18.8)
Overall SurvivalAnd the rest is history….
Cabozantinib Activity in Sunitinib-Resistant Xenografts
Cabozantinib rescues acquired resistance to sunitinib in a RCC model Efficacy with cabozantinib was associated with inhibition of MET and AXL in vivo
Saline Sunitinib only
Sunitinib
+Cabozantinib
P-AXL
AXL
P-Met
Met
Zhou and Jonasch, et al. (2015) Oncogene .
Eric Jonasch, MDACC
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The impact of Angiotensin System Inhibitors (ASIs) in mRCC
McKay, et al, Clin Cancer Res. 2015
VEGF Inh.IFN-α
A-498 RCC cell line 769-P RCC cell line
The Renin-Angiotensin System Rana McKay Ronit Simantov, Pfizer
-Using Harvard database+ IMDC Cohort + Pfizer cohort + TCGA:
Body Mass Index FASN expression
15 International Centers, 1 Pharma and 6 disciplines:
• Urology
• Medical Oncology
• Statistics
• Computational Biology (TCGA)
• Epidemiology
• Pathology
Laurence Albiges
Discipline Main Projects and work…
Fabio Schutz Med Onc MET SNP predicts recurrence in RCC, meta-
analyses of rare toxicities from TKIs
Andre Fay Med Onc mTOR pathways mutations and rapalogs, TKI
biomarkers
Guillermo DeVelasco Med Onc Biomarkers of RCC (TKI, immuneTX)
Monty Pal Med Onc Genomics of rare RCC tumors, cfDNA,
biomarkers in RCC. Also he went to college at
age 13
Quoc Trinh/Maxine Sun Urology and
Health
Service
Research
Health disparities in prostate cancer research,
Modern day application of cytoreductive
nephrectomy
Katherine Krajewski Radiology Novel radiologic biomarkers of response to TKIs
And many others: Urun,
Moreira, Lalani, Hamieh,
Mulane, Bossé….
…….. ….
Computational
Team/Broad Institute
Diana Miao
Stephanie Mullane
Eli Van Allen
The Patients
Lank Center for
GU Oncology
Joaquim Bellmunt
Rana McKay
Lauren Harshman
Mark Pomerantz
Craig Norton
Stats Team
SPORE P50 CA101942
DFCI/BWH/BIDMC/Harvard
Sabina Signoretti
Bill Kaelin
Dave McDermott
K. Mahoney
M. Giannakis
David Kwiatkowski
Gordon Freeman
Matt Freedman
US and International
collaborators
IMDC members
TCGA collaborators
Industry collaborators
Motzer
Tannir
Escudier/Albiges
Rini
Vaishampayan
Donskov
Porta
Brugarolas
Many more
Health Service Research
-Maxine Sun
-Paul Nguyen
-Steve Chang
-Quoc Trinh