Department of Medical Oncology, Hospital del Mar, Barcelona, Spain.
Nat Med. 2012 Jan 22;18(2):221-3. doi: 10.1038/nm.2609.
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.
针对表皮生长因子受体（EGFR）的抗体——西妥昔单抗和帕尼单抗——被广泛用于治疗结直肠癌。不幸的是，患者最终会对这些药物产生耐药性。我们描述了一种获得性的 EGFR 外显子突变（S492R），它阻止了西妥昔单抗的结合，并导致对西妥昔单抗的耐药性。然而，具有这种突变的细胞仍然保留与帕尼单抗的结合，并被其抑制生长。在这里研究的 10 名疾病进展后接受西妥昔单抗治疗的患者中有 2 名发生了这种突变。一名携带 S492R 突变的西妥昔单抗耐药患者对帕尼单抗治疗有反应。
