OncoTargets and Therapy (Feb 2023)
Ineffectiveness of Crizotinib in a Non-Small-Cell Lung Cancer with Novel ALK- LIMS1 Fusion: A Case Report
Abstract
Junmei Shi,1,* Zhaohui Jia,2,* Zhiguo Zhou,1 Liyan Zhao,2 Qingju Meng,2 Yibing Liu1 1Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Clinical Pharmacology, The First Affiliated Hospital of Xingtai Medical College, Xingtai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yibing Liu, Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, 12 JianKang Road, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +86-13831173220, Email [email protected] Qingju Meng, Department of Orthopedics, The First Affiliated Hospital of Xingtai Medical College, 376 Shun de Road, Qiaodong District, Xingtai, Hebei Province, People’s Republic of China, Tel +86-13780444436, Email [email protected]: Anaplastic lymphoma kinase (ALK) rearrangements have been reported in 3– 7% of non-small-cell lung cancers (NSCLC). ALK has been reported to be fused with a variety of genes in NSCLC. Significant clinical activity was achieved by ALK inhibitors in patients with NSCLC harbouring ALK translocations. We reported on a 48-year-old male Chinese patient with advanced lung adenocarcinoma harboring a novel ALK-LIMS1 who showed no response to crizotinib. The tissue was assayed by immunohistochemistry (IHC) for ALK and showed diffuse expression of ALK. Next-generation sequencing (NGS) was performed on the peripheral blood and tissue. The previous tumor tissue showed diffuse expression of ALK. Tissue and the later peripheral blood revealed a ALK- LIMS1 fusion. The patient failed to benefit from crizotinib (250 mg, twice a day), with a progression-free survival of two months. We identified a new ALK-LIMS1 fusion from an advanced lung adenocarcinoma which was primary resistant to crizotinib. Our case suggested that the coexistence of mutations and the non-dominant clone, as well as the rearrangement of ALK fusion, did not result in expressed ALK kinase domain that might lead to no response to ALK-TKIs.Keywords: non-small-cell lung cancer, next-generation sequencing, ALK- LIMS1, crizotinib
