a Samsung Biomedical Research Institute, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
b Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.
Expert Rev Mol Diagn. 2017 Oct;17(10):933-942. doi: 10.1080/14737159.2017.1372196. Epub 2017 Aug 30.
The discovery of activating genetic and their use as predictive biomarkers for targeted therapy, such as tyrosine kinase inhibitors (TKIs), has changed the treatment paradigm of non-small cell lung cancer (NSCLC). As a result, epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) TKIs have become the standard first-line treatment. Since then, other kinds of targetable oncogenic alterations have been identified in NSCLC. Several novel, molecularly-targeted TKIs have now achieved regulatory approval, while many others are currently in early- or late-phase clinical trial testing. These TKIs have significantly impacted and changed clinical outcomes for advanced NSCLC. Areas covered: In this review, the authors discuss recent evidence and progress in targeted therapies, especially small molecular tyrosine kinase inhibitors, matched with their biomarkers for the treatment of advanced NSCLC. Expert commentary: Although targeted therapies dramatically improve the outcome of patients with NSCLC harboring specific oncogenic alterations, molecular and clinical resistance almost invariably develops. New TKIs specifically active in molecular subgroups of NSCLC or the resistance setting have now been developed. The development of additional TKIs and rational combinations may further improve outcomes of NSCLC.
激活基因的发现及其作为靶向治疗（如酪氨酸激酶抑制剂[TKI]）的预测生物标志物的应用，改变了非小细胞肺癌（NSCLC）的治疗模式。因此，表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）TKI 已成为标准的一线治疗药物。此后，在 NSCLC 中又确定了其他可靶向的致癌改变。现在已有几种新型的、针对特定分子的 TKI 获得了监管批准，而许多其他 TKI 目前正在早期或晚期临床试验中进行测试。这些 TKI 显著影响并改变了晚期 NSCLC 的临床结果。涵盖领域：在这篇综述中，作者讨论了针对 NSCLC 的靶向治疗，特别是小分子酪氨酸激酶抑制剂，及其生物标志物的最新证据和进展。专家评论：虽然针对特定致癌改变的靶向治疗显著改善了 NSCLC 患者的预后，但几乎不可避免地会出现分子和临床耐药。现在已经开发出了针对 NSCLC 的特定分子亚群或耐药性的新型 TKI。额外 TKI 的开发和合理组合可能会进一步改善 NSCLC 的结果。
