Transcript 2nd Quebec Conference on Therapeutic Resistance in Cancer

2nd Quebec Conference on
Therapeutic Resistance in Cancer
Bienvenue!!!!!
Network and Partners
Members
80 members from Montréal,
Québec City and Sherbrooke
Coalition Priorité Cancer
(advocacy group)
Government
FRSQ (research)
MDEIE (economic dev.)
MSSS (health)
Q-CROC
Hospitals
Universities
Pharma
(Pfizer, Sanofi and many others)
Ongoing Q-CROC Research Projects
Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to
Standard First-Line Therapy in Patients with Metastatic Colorectal Cancer (QCROC-01)
• Needle core biopsies of liver metastasis at D0 and at acquired resistance
• Blood samples collected and banked during treatment
Biopsy-driven study in Non-Hodkins Lymphoma (NHL) using rituximab in
combination with a drug involved in epigenetic modifications (Q-CROC-02)
• Lymph node biopsies D0, D15 and optional at 24 hrs
• PBMC isolation at D0 and D15
The genomics and proteomics of Triple Negative Breast Cancer drug resistant
breast cancer (Q-CROC-03)
•Neoadjuvant: Biopsy: breast before treatment and at surgery
•Metastatic: Biopsy: liver, skin, lung, pleura; before and after treatment
Breast cancer gene expression array phenotyping can
guide therapy:
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ER+ luminal A
ER+ luminal B
HER2+
Triple negative
(ER-PR-HER2-),
basal-like
normal
This is only a first step.......
Predictive markers: WHY?
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Estrogen receptor: the oldest target and
tumor marker
Tamoxifen: discovered in 1970s
• Efficacy in ER+ breast cancers
 adjuvant
Resistance
Prognostic,
Prognostic,
biologic
biologic
factors
factors
Predictive markers: WHY?
HERCEPTIN: effective in breast cancer patients with
ERBB2 amplification (approx 15-25% breast cancer patients)
Romond E et al. N Engl J Med 2005;353:1673-1684
Kaplan-Meier Estimates of Disease-free Survival (Panel A) and Overall Survival (Panel B)
$ 50000/year
Burning questions:
WHO can be spared unnecessary treatment?
WHO will predictably not benefit?
HOW can we overcome resistance?
Focus on therapeutic resistance in the metastatic
setting
FOCUS: Metastatic disease
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Metastases are ultimately the lethal element
They are either initially or inevitably become
resistant
New treatments are almost always studied in this
setting
There are opportunties for biology discovery (e.g.
discordance between primary and metastatic
tumors, etc.)
Limited number of annotated biobanks of
metastatic tumors linked to specific therapies
FOCUS: Therapeutic resistance
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Clinically resistance is a ‘hard endpoint’…what is
stable disease?
Scientific opportunities
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The biology of intrinsic resistance vs. acquired resistance
? Stem cells
Novel mechanisms, novel cross-talk between pathways
Modifications of drugs to overcome resistance
Potential new chemosensitizers
Diagnostic tests
Personalized medicine
Because technology to facilitate it is rapidly
developing;
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Because it is scientifically and conceptually
appealing;
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Because it may be the only way to afford new
targeted agents
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It is best for the patients, since humility requires
us to recognize serious limitations in our current
approach
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Thanks to sponsors
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Canadian Institutes for Health Research:
conference grant
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Gold sponsor: Roche Canada
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Platinum Sponsor: Astra Zeneca
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And many others