The role of BIM gene deletion in ALK-mutated Non-small cell lung cancer treated with alectinib.

IF 3.5 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Experimental Medicine Pub Date : 2025-02-11 DOI:10.1007/s10238-025-01579-1

Shuang Hou, Weijun Zhang, Wei Pang, Haiqun Xia, Jinyun Tan, Qingfang Huang, Ping Yang

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Abstract

Alectinib, as a first-line therapeutic option for advanced ALK mutation-positive non-small-cell lung cancer (NSCLC), is now widely used in the clinic. However, the associated mechanisms of resistance are unknown. The first documented case of ALK-mutated NSCLC's resistance to alectinib is herein reported in relation to BIM gene deletion status. In particular, cell inhibition assay (CCK8 assay), cell transfection, fluorescence microscopy, RT-PCR, cell proliferation assay, cell migration assay and western blotting were undertaken for exploring the link between BIM status and alectinib resistance. Clinical cases showed that the BIM gene was absent in alectinib-resistant tumor tissues. Further experimental validation yielded that NSCLC with deleted BIM genes were less sensitive to aleitinib. BIM gene deletion can increase resistance to alectinib, and the potential efficacy of a combination of BIM sensitizer and alectinib to overcome alectinib resistance can be explored.

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BIM基因缺失在阿来替尼治疗ALK突变非小细胞肺癌中的作用

Alectinib作为晚期ALK突变阳性非小细胞肺癌（NSCLC）的一线治疗选择，现已广泛应用于临床。然而，相关的耐药机制尚不清楚。本文报道了第一例alk突变的非小细胞肺癌对alectinib的耐药性与BIM基因缺失状态的关系。特别是通过细胞抑制实验（CCK8实验）、细胞转染、荧光显微镜、RT-PCR、细胞增殖实验、细胞迁移实验和western blotting来探索BIM状态与alectinib耐药性之间的联系。临床病例显示，BIM基因在阿勒替尼耐药肿瘤组织中缺失。进一步的实验验证表明，BIM基因缺失的NSCLC对阿利替尼的敏感性较低。BIM基因缺失可增加对阿勒替尼的耐药性，可以探索BIM敏化剂与阿勒替尼联合使用克服阿勒替尼耐药性的潜在疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Experimental Medicine 医学-医学：研究与实验

CiteScore

4.80

自引率

2.20%

发文量

159

审稿时长

2.5 months

期刊介绍： Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.