Resistance to EGFR targeted antibodies - expansion of clones present from the start of treatment. The more things change, the more they stay the same (Plus ca change, plus ca ne change pas!)

The management of metastatic colorectal cancer (mCRC) has evolved with the development of targeted therapies. Two monoclonal antibodies, panitumumab and cetuximab, directed against the epidermal growth factor receptor (EGFR), have efficacy either in combination with chemotherapy or alone in the chemotherapy-refractory setting (1-3).

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[2]  F. Bosch,et al.  Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer , 2012, Nature Medicine.

[3]  Daniel J. Freeman,et al.  Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  P. Jänne,et al.  OP 85 Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab , 2011 .

[5]  Dongsheng Tu,et al.  Cetuximab for the treatment of colorectal cancer. , 2007, The New England journal of medicine.

[6]  Johannes G. Reiter,et al.  The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers , 2012, Nature.

[7]  Niels Pallisgaard,et al.  Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan , 2012, Clinical Cancer Research.

[8]  Enzo Medico,et al.  Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer , 2012, Nature.

[9]  Sabine Tejpar,et al.  KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. , 2011, The Lancet. Oncology.

[10]  Armando Santoro,et al.  Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. , 2004, The New England journal of medicine.

[11]  Dongsheng Tu,et al.  K-ras mutations and benefit from cetuximab in advanced colorectal cancer. , 2008, The New England journal of medicine.

[12]  Emma Donald,et al.  Comparison of KRAS Mutation Assessment in Tumor DNA and Circulating Free DNA in Plasma and Serum Samples , 2012, Clinical medicine insights. Pathology.

[13]  Marc Peeters,et al.  Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.