Primary resistance to first- and second-generation ALK inhibitors in a non-small cell lung cancer patient with coexisting ALK rearrangement and an ALK F1174L-cis-S1189C de novo mutation: A case report

Jiuzhou Zhao; Xiang Li; Ruizhe Fan; Yaping Qin; Zhizhong Wang; Bo Wang; Shaomei Li; Jianfeng Fan; Xinxin Wu; Hongxia Liu; Yuping Guan; Yinfeng Liang; Xiao Zhang; Yongjun Guo

doi:10.3389/fphar.2022.1060460

Primary resistance to first- and second-generation ALK inhibitors in a non-small cell lung cancer patient with coexisting ALK rearrangement and an ALK F1174L-cis-S1189C de novo mutation: A case report

Front Pharmacol. 2022 Nov 23:13:1060460. doi: 10.3389/fphar.2022.1060460. eCollection 2022.

Authors

Jiuzhou Zhao^{1

2}, Xiang Li¹, Ruizhe Fan¹, Yaping Qin³, Zhizhong Wang^{1

2}, Bo Wang^{1

2}, Shaomei Li⁴, Jianfeng Fan⁵, Xinxin Wu^{1

2}, Hongxia Liu^{1

2}, Yuping Guan¹, Yinfeng Liang¹, Xiao Zhang⁴, Yongjun Guo^{1

2}

Affiliations

¹ Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
² Henan Key Laboratory of Molecular Pathology, Zhengzhou, China.
³ School of Basic Medical Sciences, Academy of Medical Sciences, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
⁴ Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
⁵ Department of Medical Imaging, Zhenping People's Hospital, Nanyang, China.

Abstract

The effectiveness of the tyrosine kinase inhibitor ALK (TKI) for non-small cell lung cancer has been confirmed. However, resistance to ALK-TKIs seems inevitable. Mutations in the ALK kinase domain have been reported as an important mechanism of acquired resistance to ALK therapy. However, patients with de novo ALK kinase domain mutations and ALK rearrangements who were not treated with ALK inhibitors have rarely been reported. Here, we report a case of primary drug resistance to first- and second-generation ALK inhibitors in a NSCLC patient with ALK-rearrangement. The next-generation sequencing test of the pathological biopsy showed that the de novo ALK kinase domain mutation F1174L-cis-S1189C may be the cause of primary drug resistance.

Keywords: EML4-ALK; F1174L; S1189C; de novo mutation; next generation sequencing (NGS); non-small cell lung cancer (NSCLC).

Publication types

Case Reports