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Oltre RAS e RAF quali altri fattori predittivi di risposta e Oltre - - PowerPoint PPT Presentation
Oltre RAS e RAF quali altri fattori predittivi di risposta e Oltre - - PowerPoint PPT Presentation
Mario Scartozzi Clinica di Oncologia Medica Clinica di Oncologia Medica Ancona Oltre RAS e RAF quali altri fattori predittivi di risposta e Oltre RAS e RAF, quali altri fattori predittivi di risposta e prognostici? Quali evidenze, quali
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Potential Markers for Colon Cancer Receiving “OLD” chemotherapy regimens py g Drug Marker Fluoropyrimidines TS DPD* TP MTHFR Fluoropyrimidines TS, DPD*, TP, MTHFR expression/polymorphisms i G l hi * Irinotecan UGT polymorphisms*, transporter polymorphisms Oxaliplatin ERCC1, GST P1, XPD expression, transporter polymorphisms *FDA-recognized FDA recognized
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HER‐3, IGF‐1 as Molecular TARGETs HER 3 HER-3 U3-1287-AMG888 MM 121 MM-121 MEHD7945A (Dual EGFR & HER-3) IGF-1R IMC A12 IMC-A12 R1507 MK 0646 MK-0646 AMG-479
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Receptor AMPLIFICATION & CROSS‐TALK..!
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2011
Randomised phase II/III study in K-RAS wt refractory CRC (dalotuzumab -ab anti IGFR1-irinotecan-cetuximab)
100
g
/k 10 mg/kg 75
survivin
Control 7.5 mg/kg 50 25
portion s
25
Prop
12 96 24 60 72 84 36 48 Weeks
Watkins et al.
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2012
Watkins et al.2012
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2013
Molecular biomarkers for a prognostic stratification of K- RAS wild type colorectal cancer patients receiving y g irinotecan-cetuximab.
Scartozzi M et Al AIRC IG N-11-704
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2013
Molecular biomarkers for a prognostic stratification of K- RAS wild type colorectal cancer patients receiving y g irinotecan-cetuximab.
Scartozzi M et Al AIRC IG N-11-704
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2013
Molecular biomarkers for a prognostic stratification of K-RAS wild type colorectal cancer patients receiving y g irinotecan-cetuximab.
Scartozzi M et Al AIRC IG N-11-704
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Misale S et Al, Nature 2012
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Misale S et Al, Nature 2012
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K‐RAS gene alterations & acquired RESISTANCE
# Total Patients # Patients who develop KRAS mutations/amplification at resistance % Misale et al., 2012 11 7 63.6% Diaz et al 2012 28 13 46% Diaz et al., 2012 28 13 46%
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NEXT in our PRACTICE?
Vilar E e Tabernero J, Nature 2012
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Resistance to BEVA: announced event?
Kopetz S et al JCO 2010
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