Antibodies against epidermal growth factor receptor (EGFR)--cetuximab and panitumumab--are widely used to treat colorectal cancer. Unfortunately, patients eventually develop resistance to these agents. We describe an acquired EGFR ectodomain mutation (S492R) that prevents cetuximab binding and confers resistance to cetuximab. Cells with this mutation, however, retain binding to and are growth inhibited by panitumumab. Two of ten subjects studied here with disease progression after cetuximab treatment acquired this mutation. A subject with cetuximab resistance harboring the S492R mutation responded to treatment with panitumumab.
Pubmed ID: 22270724 RIS Download
Mesh terms: Antibodies, Monoclonal | Antibodies, Monoclonal, Humanized | Antineoplastic Agents | Cell Line, Tumor | Cetuximab | Colorectal Neoplasms | Drug Resistance, Neoplasm | Epitopes | Humans | Mutation, Missense | Quinazolines | Receptor, Epidermal Growth Factor
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