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Journal Article

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

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons50203

Himmelbauer,  Heinz
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Montagut, C., Dalmases, A., Bellosillo, B., Crespo, M., Pairet, S., Iglesias, M., et al. (2012). Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer. Nature Medicine, 18(2), 221-223. doi:10.1038/nm.2609.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-F076-1
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.