{"title":"The role of BIM gene deletion in ALK-mutated Non-small cell lung cancer treated with alectinib.","authors":"Shuang Hou, Weijun Zhang, Wei Pang, Haiqun Xia, Jinyun Tan, Qingfang Huang, Ping Yang","doi":"10.1007/s10238-025-01579-1","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"54"},"PeriodicalIF":3.2000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10238-025-01579-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
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.
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.
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