hide
Free keywords:
Antibodies, Monoclonal/*therapeutic use
Antineoplastic Agents/*therapeutic use
Cell Line, Tumor
Colorectal Neoplasms/*drug therapy/genetics
Drug Resistance, Neoplasm/*genetics
Epitopes/genetics
Humans
Mutation, Missense/genetics
Quinazolines/therapeutic use
Receptor, Epidermal Growth Factor/*genetics
Abstract:
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.
