Guo Yijia, Song Jun, Wang Yanru, Huang Letian, Sun Li, Zhao Jianzhu, Zhang Shuling, Jing Wei, Ma Jietao, Han Chengbo
Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
Front Oncol. 2020 Dec 10;10:610923. doi: 10.3389/fonc.2020.610923. eCollection 2020.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) greatly improve the survival and quality of life of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, many patients exhibit or primary/early resistance. In addition, patients who initially respond to EGFR-TKIs exhibit marked diversity in clinical outcomes. With the development of comprehensive genomic profiling, various mutations and concurrent (, coexisting) genetic alterations have been discovered. Many studies have revealed that concurrent genetic alterations play an important role in the response and resistance of EGFR-mutant NSCLC to EGFR-TKIs. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on EGFR-TKI treatment efficacy is necessary. Further exploration of other biomarkers that can predict EGFR-TKI efficacy will help clinicians identify patients who may not respond to TKIs and allow them to choose appropriate treatment strategies. Here, we review the literature on specific gene alterations that coexist with EGFR mutations, including common alterations (intra-EGFR [on target] co-mutation, TP53, PIK3CA, and PTEN) and driver gene alterations (ALK, KRAS, ROS1, and MET). We also summarize data for other biomarkers (, PD-L1 expression and BIM polymorphisms) associated with EGFR-TKI efficacy.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）极大地提高了具有EGFR突变的非小细胞肺癌（NSCLC）患者的生存率和生活质量。然而，许多患者会出现获得性或原发性/早期耐药。此外，最初对EGFR-TKIs有反应的患者在临床结局上表现出显著差异。随着综合基因组分析的发展，已发现各种突变和并发（共存）基因改变。许多研究表明，并发基因改变在EGFR突变的NSCLC对EGFR-TKIs的反应和耐药中起重要作用。为了优化临床结局，有必要更好地了解特定的并发基因改变及其对EGFR-TKI治疗疗效的影响。进一步探索其他可预测EGFR-TKI疗效的生物标志物将有助于临床医生识别可能对TKIs无反应的患者，并使他们能够选择合适的治疗策略。在此，我们综述了与EGFR突变共存的特定基因改变的文献，包括常见改变（EGFR内部[靶向]共突变、TP53、PIK3CA和PTEN）和驱动基因改变（ALK、KRAS、ROS1和MET）。我们还总结了与EGFR-TKI疗效相关的其他生物标志物（PD-L1表达和BIM多态性）的数据。
