Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer

Clara Montagut, Alba Dalmases, Beatriz Bellosillo, Marta Crespo, Silvia Pairet, Mar Iglesias, Marta Salido, Manuel Gallen, Scot Marsters, Siao Ping Tsai, André Minoche, Seshagiri Somasekar, Sergi Serrano, Heinz Himmelbauer, Joaquim Bellmunt, Ana Rovira, Jeff Settleman, Francesc Bosch, Joan Albanell

Research output: Contribution to journalArticleResearchpeer-review

308 Citations (Scopus)

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. © 2012 Nature America, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)221-223
JournalNature Medicine
Volume18
Issue number2
DOIs
Publication statusPublished - 22 Jan 2012

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