Xue Yinyin, Li Wen, Huang Kaili, Zhou Qinghua, Wu Qiang
Department of Radiation Oncology Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Pharmacol. 2025 Aug 11;16:1602654. doi: 10.3389/fphar.2025.1602654. eCollection 2025.
Anaplastic lymphoma kinase (ALK) rearrangement is a crucial oncogenic driver in non-small cell lung cancer (NSCLC). ALK tyrosine kinase inhibitors (ALK-TKIs) represent the primary therapeutic option for advanced NSCLC patients with ALK rearrangements. However, the definitive determination of ALK-TKIs sensitivity towards newly identified rare ALK rearrangements remains elusive. Herein, we present a patient with lung adenocarcinoma harboring a novel ALK rearrangement who exhibited major pathological response (MPR) following neoadjuvant treatment with alectinib.
We conduct immunohistochemistry (IHC) staining with Ventana with D5F3 clone, fluorescence hybridization (FISH, The Vysis ALK Break Apart FISH Probe Kit), and next-generation sequencing (NGS) analyses (Burning Rock, Guangzhou, China) on biopsy sample obtained from the patient.
The patient, a 66-year-old female, was diagnosed with stage IIIB-N3 adenocarcinoma in the right upper lobe of the lung. NGS testing revealed a previously unreported MIR217HG-ALK rearrangement, which was subsequently confirmed by IHC and FISH. Following 5 months of neoadjuvant treatment with alectinib, the patient underwent the right upper lobectomy and achieved MPR, resulting in disease-free survival (DFS) exceeding 19 months.
In this study, we present the first documented case of a patient with lung adenocarcinoma harboring a novel MIR217HG-ALK rearrangement who exhibited favorable response to neoadjuvant alectinib. Our findings suggest that alectinib holds promise as an efficacious therapeutic option for individuals with MIR217HG-ALK rearranged lung adenocarcinoma, thereby offering valuable insights for the clinical management of these patients.
间变性淋巴瘤激酶(ALK)重排是非小细胞肺癌(NSCLC)中一个关键的致癌驱动因素。ALK酪氨酸激酶抑制剂(ALK-TKIs)是晚期ALK重排NSCLC患者的主要治疗选择。然而,对于新发现的罕见ALK重排,ALK-TKIs敏感性的明确判定仍然难以捉摸。在此,我们报告一例肺腺癌患者,其携带一种新的ALK重排,在接受阿来替尼新辅助治疗后出现了主要病理缓解(MPR)。
我们对从该患者获取的活检样本进行了使用Ventana的D5F3克隆的免疫组织化学(IHC)染色、荧光原位杂交(FISH,Vysis ALK Break Apart FISH探针试剂盒)以及二代测序(NGS)分析(广州燃石医学)。
该患者为一名66岁女性,被诊断为右肺上叶IIIB-N3期腺癌。NGS检测发现一种此前未报道的MIR217HG-ALK重排,随后经IHC和FISH证实。在接受5个月的阿来替尼新辅助治疗后,该患者接受了右上肺叶切除术并实现了MPR,无病生存期(DFS)超过19个月。
在本研究中,我们报告了首例有记录的携带新的MIR217HG-ALK重排的肺腺癌患者对阿来替尼新辅助治疗表现出良好反应的病例。我们的研究结果表明,阿来替尼有望成为MIR217HG-ALK重排肺腺癌患者的有效治疗选择,从而为这些患者的临床管理提供有价值的见解。