Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations.
10.1016/j.apsb.2023.03.007
- Author:
Chen SHI
1
;
Cong ZHANG
1
;
Zhiwen FU
1
;
Jinmei LIU
1
;
Yuanfeng ZHOU
2
;
Bao CHENG
3
;
Cong WANG
1
;
Shijun LI
1
;
Yu ZHANG
1
Author Information
1. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
2. Department of Preclinical Translational Science, Shanghai Hansoh Biomedical Co., Ltd., Shanghai 201203, China.
3. Department of Chemistry, Shanghai Hansoh Biomedical Co., Ltd., Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
Anti-tumor activity;
Aumolertinib;
EGFR tyrosine kinase inhibitor;
Exon 20 insertion;
Non-small cell lung cancer;
Oncology;
Targeted therapy;
Uncommon EGFR mutations
- From:
Acta Pharmaceutica Sinica B
2023;13(6):2613-2627
- CountryChina
- Language:English
-
Abstract:
Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%-20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.
