Journal
NATURE MEDICINE
Volume 18, Issue 2, Pages 221-223Publisher
NATURE RESEARCH
DOI: 10.1038/nm.2609
Keywords
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Funding
- Institut de Salud Carlos III (ISCIII) -Subdireccion General de Evaluacion y Fomento de la Investigacion [PS09/01491, PI08/0211, PI09/1285]
- Plan Nacional (PN) de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I), iniciativa Ingenio, programa Consolider
- ISCIII/FEDER [RD06/0020/0109]
- PN de I+D+I [2008-20011]
- DIUE Generalitat de Catalunya [2009 SGR 321]
- FEDER [RD09/0076/00036]
- Xarxa de Bancs de Tumors de Catalunya
- PDO (XBTC)
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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.
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