Nurwidya Fariz, Takahashi Fumiyuki, Murakami Akiko, Kobayashi Isao, Kato Motoyasu, Shukuya Takehito, Tajima Ken, Shimada Naoko, Takahashi Kazuhisa
Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan.
Respir Investig. 2014 Mar;52(2):82-91. doi: 10.1016/j.resinv.2013.07.007. Epub 2013 Aug 30.
Activation of epidermal growth factor receptor (EGFR) triggers anti-apoptotic signaling, proliferation, angiogenesis, invasion, metastasis, and drug resistance, which leads to development and progression of human epithelial cancers, including non-small cell lung cancer (NSCLC). Inhibition of EGFR by tyrosine kinase inhibitors such as gefitinib and erlotinib has provided a new hope for the cure of NSCLC patients. However, acquired resistance to gefitinib and erlotinib via EGFR-mutant NSCLC has occurred through various molecular mechanisms such as T790M secondary mutation, MET amplification, hepatocyte growth factor (HGF) overexpression, PTEN downregulation, epithelial-mesenchymal transition (EMT), and other mechanisms. This review will discuss the biology of receptor tyrosine kinase inhibition and focus on the molecular mechanisms of acquired resistance to tyrosine kinase inhibitors of EGFR-mutant NSCLC.
表皮生长因子受体（EGFR）的激活会触发抗凋亡信号传导、增殖、血管生成、侵袭、转移和耐药性，从而导致包括非小细胞肺癌（NSCLC）在内的人类上皮癌的发生和发展。吉非替尼和厄洛替尼等酪氨酸激酶抑制剂对EGFR的抑制为NSCLC患者的治愈带来了新希望。然而，EGFR突变的NSCLC对吉非替尼和厄洛替尼产生获得性耐药是通过多种分子机制发生的，如T790M二次突变、MET扩增、肝细胞生长因子（HGF）过表达、PTEN下调、上皮-间质转化（EMT）及其他机制。本综述将讨论受体酪氨酸激酶抑制的生物学特性，并重点关注EGFR突变的NSCLC对酪氨酸激酶抑制剂获得性耐药的分子机制。
