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 speranze?
LA NATURA DELLE COSE DAL PARTICOLARE ALL’UNIVERSALE
Potential Markers for Colon Cancer Receiving “OLD” chemotherapy regimens py g Drug Marker Fluoropyrimidines Fluoropyrimidines TS DPD* TP MTHFR TS, DPD*, TP, MTHFR expression/polymorphisms Irinotecan i UGT polymorphisms*, transporter G l hi * polymorphisms Oxaliplatin ERCC1, GST P1, XPD expression, transporter polymorphisms *FDA-recognized FDA recognized
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
Receptor AMPLIFICATION & CROSS ‐ TALK..!
2011 Randomised phase II/III study in K-RAS wt refractory CRC (dalotuzumab -ab anti IGFR1-irinotecan-cetuximab) 100 10 mg/kg g survivin 7.5 mg/kg /k 75 Control portion s 50 Prop 25 25 0 0 0 12 24 36 48 60 72 84 96 Weeks Watkins et al.
2012 Watkins et al.2012
2013 Molecular biomarkers for a prognostic stratification of K- RAS wild type y colorectal cancer patients receiving g irinotecan-cetuximab. AIRC IG N-11-704 Scartozzi M et Al
2013 Molecular biomarkers for a prognostic stratification of K- RAS wild type y colorectal cancer patients receiving g irinotecan-cetuximab. AIRC IG N-11-704 Scartozzi M et Al
2013 Molecular biomarkers for a prognostic stratification of K-RAS wild type colorectal cancer patients receiving y g irinotecan-cetuximab. AIRC IG N-11-704 Scartozzi M et Al
Misale S et Al, Nature 2012
Misale S et Al, Nature 2012
K ‐ RAS gene alterations & acquired RESISTANCE # Total # Patients who develop KRAS Patients mutations/amplification at resistance % Misale et al., 2012 11 7 63.6% Diaz et al Diaz et al., 2012 2012 28 28 13 13 46% 46%
NEXT in our PRACTICE? Vilar E e Tabernero J, Nature 2012
Resistance to BEVA: announced event? Kopetz S et al JCO 2010
Receptor AMPLIFICATION & CROSS ‐ TALK..! Giampieri R, Aprile G et Al, Curr Drug targets 2014
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