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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

Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Zhao, Jiuzhou;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Li, Xiang;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Fan, Ruizhe;
Affiliation
School of Basic Medical Sciences ,Academy of Medical Sciences ,Henan Institute of Medical and Pharmaceutical Sciences ,Zhengzhou University ,Zhengzhou ,Henan ,China
Qin, Yaping;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Wang, Zhizhong;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Wang, Bo;
Affiliation
Department of Medical Oncology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Li, Shaomei;
Affiliation
Department of Medical Imaging ,Zhenping People’s Hospital ,Nanyang ,China
Fan, Jianfeng;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Wu, Xinxin;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Liu, Hongxia;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Guan, Yuping;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Liang, Yinfeng;
Affiliation
Department of Medical Oncology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Zhang, Xiao;
Affiliation
Department of Molecular Pathology ,The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital ,Zhengzhou ,China
Guo, Yongjun

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.

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License Holder: Copyright © 2022 Zhao, Li, Fan, Qin, Wang, Wang, Li, Fan, Wu, Liu, Guan, Liang, Zhang and Guo.

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