Wang Shuhang, Tsui Stella T, Liu Christina, Song Yongping, Liu Delong
The Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing, China.
SUNY Stony Brook University, Stony Brook, NY, 11794, USA.
J Hematol Oncol. 2016 Jul 22;9(1):59. doi: 10.1186/s13045-016-0290-1.
T790M mutation is the most common mechanism for resistance to first- and second-generation tyrosine kinase inhibitors (TKI) for epidermal growth factor receptor (EGFR). Several third-generation EGFR mutant selective TKIs are being explored to conquer this resistance. AZD9291 (osimertinib, tagrisso) has been approved for treatment of the metastatic EGFR T790M mutation-positive non-small cell lung cancer. Resistance to AZD9291 has been described. C797S mutation was reported to be a major mechanism for resistance to T790M-targeting EGFR inhibitors. This review summarizes the latest development in identifying the C797S mutation and EAI045, the novel selective inhibitor overcoming the C797S mutant.
T790M突变是表皮生长因子受体（EGFR）对第一代和第二代酪氨酸激酶抑制剂（TKI）耐药的最常见机制。目前正在探索几种第三代EGFR突变选择性TKI来克服这种耐药性。AZD9291（奥希替尼，泰瑞沙）已被批准用于治疗转移性EGFR T790M突变阳性非小细胞肺癌。已有对AZD9291耐药的报道。据报道，C797S突变是对靶向T790M的EGFR抑制剂耐药的主要机制。本综述总结了在鉴定C797S突变以及克服C797S突变的新型选择性抑制剂EAI045方面的最新进展。
