O'Kane Grainne M, Bradbury Penelope A, Feld Ronald, Leighl Natasha B, Liu Geoffrey, Pisters Katherine-M, Kamel-Reid Suzanne, Tsao Ming S, Shepherd Frances A
Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada.
Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada.
Lung Cancer. 2017 Jul;109:137-144. doi: 10.1016/j.lungcan.2017.04.016. Epub 2017 Apr 27.
Molecular profiling in advanced non-small cell lung cancer (NSCLC) has allowed for the detection of actionable mutations, which has revolutionized the treatment paradigm in this highly fatal disease. Mutations involving the epidermal growth factor receptor (EGFR) gene are most common and the 'classical mutations', exon 19 deletions and the point mutation L858R at exon 21, predict response to EGFR tyrosine kinase inhibitors (TKIs). The 'uncommon' EGFR mutations account for 10-18% of all EGFR mutations and primarily consist of exon 20 insertions, exon 18 point mutations and complex mutations. Improved detection techniques have broadened the spectrum of reported aberrations within the 'uncommon group' but response to TKIs is variable and not fully elucidated. This review provides an overview of the biology and incidence of uncommon EGFR mutations and summarizes reported outcomes when treated with EGFR-TKIs.
晚期非小细胞肺癌（NSCLC）的分子谱分析已能够检测出可靶向治疗的突变，这彻底改变了这种高致死性疾病的治疗模式。涉及表皮生长因子受体（EGFR）基因的突变最为常见，“经典突变”，即外显子19缺失和外显子21的L858R点突变，可预测对EGFR酪氨酸激酶抑制剂（TKIs）的反应。“罕见”EGFR突变占所有EGFR突变的10%-18%，主要包括外显子20插入、外显子18点突变和复杂突变。改进的检测技术拓宽了“罕见组”中已报道的畸变谱，但对TKIs的反应各不相同且尚未完全阐明。本综述概述了罕见EGFR突变的生物学特性和发生率，并总结了用EGFR-TKIs治疗时已报道的结果。
