• Clin Colorectal Cancer · Dec 2011

    Is there a role for IGF1R and c-MET pathways in resistance to cetuximab in metastatic colorectal cancer?

    • Alessandro Inno, Mariantonietta Di Salvatore, Tonia Cenci, Maurizio Martini, Armando Orlandi, Antonia Strippoli, Anna Maria Ferrara, Cinzia Bagalà, Alessandra Cassano, Luigi Maria Larocca, and Carlo Barone.
    • Division of Medical Oncology, Catholic University of the Sacred Heart, Rome, Italy.
    • Clin Colorectal Cancer. 2011 Dec 1; 10 (4): 325-32.

    BackgroundThe KRAS mutation is not responsible for all cases of resistance to anti-epidermal growth factor receptors (EGFRs) in metastatic colorectal cancer (mCRC), and new predictive and prognostic factors are actively being sought.Patients And MethodsWe retrospectively evaluated the efficacy of a cetuximab-containing treatment in 73 patients with mCRC according to KRAS and BRAF mutational status as well as PTEN, c-MET, and insulin-like growth factor receptor (IGF1R) expression.ResultsOverall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) were significantly lower in patients with KRAS mutation than in patients with KRAS wild-type; among the population with KRAS wild-type, only 2 patients with BRAF mutations were found and neither of them achieved a response. No significant association was found between PTEN and clinical outcome. Compared with low/normal expression, c-MET overexpression significantly correlated with shorter mPFS and mOS: 3 vs. 5 months (P = .018) and 11 vs. 10 months (P = .037), respectively. In patients with high IGF1R expression, mOS was significantly longer than in those with low/normal expression (14 vs. 8 months; P = .015).ConclusionKRAS mutation significantly correlates with a worse outcome in patients treated with cetuximab, whereas no definitive inference can be drawn about the role of BRAF mutation and PTEN loss of expression. Instead, c-MET overexpression might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy. Interestingly, IGF1R overexpression seems a favorable prognostic factor in mCRC.Copyright © 2011 Elsevier Inc. All rights reserved.

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