1 Department of Biomedicine, Aarhus University, Aarhus, Denmark ; 2 Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Transl Lung Cancer Res. 2016 Apr;5(2):172-82. doi: 10.21037/tlcr.2016.04.07.
Inhibition of the epidermal growth factor receptor (EGFR) is an important strategy when treating non-small cell lung cancer (NSCLC) patients. However, intrinsic resistance or development of resistance during the course of treatment constitutes a major challenge. The knowledge on EGFR-directed tyrosine kinase inhibitors (TKIs) and their biological effect keeps increasing. Within the group of patients with EGFR mutations some benefit to a much higher degree than others, and for patients lacking EGFR mutations a subset experience an effect. Up to 70% of patients with EGFR mutations and 10-20% of patients without EGFR mutations initially respond to the EGFR-TKI erlotinib, but there is a severe absence of good prognostic markers. Despite initial effect, all patients acquire resistance to EGFR-TKIs. Multiple mechanisms have implications in resistance development, but much is still to be explored. Epithelial to mesenchymal transition (EMT) is a transcriptionally regulated phenotypic shift rendering cells more invasive and migratory. Within the EMT process lays a need for external or internal stimuli to give rise to changes in central signaling pathways. Expression of mesenchymal markers correlates to a bad prognosis and an inferior response to EGFR-TKIs in NSCLC due to the contribution to a resistant phenotype. A deeper understanding of the role of EMT in NSCLC and especially in EGFR-TKI resistance-development constitute one opportunity to improve the benefit of TKI treatment for the individual patient. Many scientific studies have linked the EMT process to EGFR-TKI resistance in NSCLC and our aim is to review the role of EMT in both intrinsic and acquired resistance to EGFR-TKIs.
抑制表皮生长因子受体（EGFR）是治疗非小细胞肺癌（NSCLC）患者的重要策略。然而，内在的耐药性或治疗过程中的耐药性发展是一个主要的挑战。关于 EGFR 定向酪氨酸激酶抑制剂（TKI）及其生物学效应的知识不断增加。在 EGFR 突变的患者群体中，一些患者受益程度远高于其他患者，而缺乏 EGFR 突变的患者中有一部分也受益。多达 70%的 EGFR 突变患者和 10-20%的无 EGFR 突变患者最初对 EGFR-TKI 厄洛替尼有反应，但缺乏良好的预后标志物。尽管最初有效果，但所有患者最终都会对 EGFR-TKI 产生耐药性。多种机制与耐药性的发展有关，但仍有许多需要探索。上皮间质转化（EMT）是一种转录调控的表型转换，使细胞更具侵袭性和迁移性。在 EMT 过程中，需要外部或内部刺激来引发中央信号通路的变化。间充质标志物的表达与 NSCLC 中的不良预后和对 EGFR-TKI 的反应不良相关，这是因为它有助于产生耐药表型。更深入地了解 EMT 在 NSCLC 中的作用，特别是在 EGFR-TKI 耐药性发展中的作用，是提高个体患者 TKI 治疗效果的机会之一。许多科学研究已经将 EMT 过程与 NSCLC 中的 EGFR-TKI 耐药性联系起来，我们的目的是回顾 EMT 在 EGFR-TKI 内在和获得性耐药中的作用。
