Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Lung Cancer. 2013 Jun;80(3):235-41. doi: 10.1016/j.lungcan.2013.01.018. Epub 2013 Feb 26.
Therapy targeted against the epidermal growth factor receptor (EGFR) has demonstrated dramatic tumor responses and favorable clinical outcomes in a select group of non-small cell lung cancer (NSCLC) patients whose tumors harbor EGFR activating mutations. The best characterized of the mutations conferring sensitivity to EGFR tyrosine kinase inhibitors (TKIs) are deletions in exon 19 and a point mutation in exon 21 (L858R). Likewise, the most common mutation that confers resistance is the T790M point mutation. However several other mutations have been reported and several have been characterized as regards their role in sensitivity or resistance to EGFR TKIs. Resistance to the EGFR TKIs erlotinib and gefitinib, and the newer irreversible EGFR TKIs is a problem of fundamental importance. Recognition of the presence and significance of specific EGFR mutations is important for appropriate therapeutic implementation of EGFR TKIs and research and development of mutation-specific inhibitors. We summarize the literature and present an overview of the subject of less common EGFR mutations and their clinical significance, with an emphasis on EGFR TKI sensitivity or resistance.
针对表皮生长因子受体 (EGFR) 的治疗在一组特定的非小细胞肺癌 (NSCLC) 患者中显示出了显著的肿瘤反应和良好的临床结果，这些患者的肿瘤携带有 EGFR 激活突变。最具特征的突变是外显子 19 的缺失和外显子 21 (L858R) 的点突变，这些突变赋予了对 EGFR 酪氨酸激酶抑制剂 (TKI) 的敏感性。同样，最常见的突变是 T790M 点突变，它赋予了耐药性。然而，已经报道了其他几种突变，并且已经对它们在 EGFR TKI 敏感性或耐药性中的作用进行了特征描述。对 EGFR TKI 厄洛替尼和吉非替尼以及更新的不可逆 EGFR TKI 的耐药性是一个具有根本重要性的问题。识别特定 EGFR 突变的存在和意义对于 EGFR TKI 的适当治疗实施以及突变特异性抑制剂的研究和开发非常重要。我们总结了文献，概述了不太常见的 EGFR 突变及其临床意义，重点介绍了 EGFR TKI 的敏感性或耐药性。
