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Nat Med. 2012 Jan 22;18(2):221-3. doi: 10.1038/nm.2609.

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

Author information

1
Department of Medical Oncology, Hospital del Mar, Barcelona, Spain.

Erratum in

  • Nat Med. 2012 Sep;18(9):1445. Somasekar, Seshagiri [corrected to Seshagiri, Somasekar].

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.

PMID:
22270724
DOI:
10.1038/nm.2609
[Indexed for MEDLINE]

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