Zhang Haijun
Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China.
Onco Targets Ther. 2016 Sep 6;9:5489-93. doi: 10.2147/OTT.S114722. eCollection 2016.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the evidence-based first-line treatment for advanced non-small-cell lung cancer that harbors sensitizing EGFR mutations (EGFRm(+)) such as exon 19 deletions and L858R substitutions in exon 21. However, acquired resistance to EGFR TKIs is mostly driven by a second-site EGFR T790M mutation, which negates their inhibitory activity. Osimertinib (AZD9291, Tagrisso™), an oral, third-generation EGFR TKI, has been designed to target the EGFR T790M mutation, while sparing wild-type EGFR. In this up-to-date review, focus is not only on the structure, mechanisms, and pharmacokinetics of osimertinib but also on summarizing clinical trials and making recommendations of osimertinib for patients with non-small-cell lung cancer.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）是针对具有敏感EGFR突变（EGFRm(+)）（如外显子19缺失和外显子21中的L858R替代）的晚期非小细胞肺癌的循证一线治疗药物。然而，对EGFR TKIs的获得性耐药主要由第二位点的EGFR T790M突变驱动，这使其失去了抑制活性。奥希替尼（AZD9291，泰瑞沙™）是一种口服的第三代EGFR TKI，其设计目的是靶向EGFR T790M突变，同时保留野生型EGFR。在这篇最新综述中，不仅关注奥希替尼的结构、作用机制和药代动力学，还总结了临床试验并对非小细胞肺癌患者使用奥希替尼提出建议。
