title: Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer.
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.
authors.affiliation: Department of Medical Oncology, Hospital del Mar, Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
authors.forename: Alba
authors.initials: A
authors.lastname: Dalmases
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Marta
authors.initials: M
authors.lastname: Crespo
authors.forename: Silvia
authors.initials: S
authors.lastname: Pairet
authors.forename: Mar
authors.initials: M
authors.lastname: Iglesias
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
authors.forename: Manuel
authors.initials: M
authors.lastname: Gallen
authors.forename: Scot
authors.initials: S
authors.lastname: Marsters
authors.forename: Siao Ping
authors.initials: SP
authors.lastname: Tsai
authors.forename: André
authors.initials: A
authors.lastname: Minoche
authors.forename: Somasekar
authors.initials: S
authors.lastname: Seshagiri
authors.forename: Seshagiri
authors.initials: S
authors.lastname: Somasekar
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
authors.forename: Heinz
authors.initials: H
authors.lastname: Himmelbauer
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Ana
authors.initials: A
authors.lastname: Rovira
authors.forename: Jeff
authors.initials: J
authors.lastname: Settleman
authors.forename: Francesc
authors.initials: F
authors.lastname: Bosch
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000939:Epitopes / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D000077156:Gefitinib; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics; D000077544:Panitumumab; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000939:Epitopes; D011799:Quinazolines; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab; D000077156:Gefitinib