未经证实:间变性淋巴瘤激酶(ALK)阳性的非小细胞肺癌(NSCLC)是一种异质性疾病。迄今为止,已经发现超过90种ALK融合在肺癌中。这里,我们首次报道了NSCLC中罕见的LOC388942-ALK融合蛋白对克唑替尼敏感,但对序贯的ceritinib和alectinib耐药,并在长期接受安洛替尼治疗后获得经典ALKG1202R耐药突变.该案例强调了在抗肿瘤过程中使用下一代测序(NGS)动态监测基因改变是必要的。
未经授权:一名55岁的男性,无吸烟史,无家族癌症史,左肺发现恶性胸腔积液和多发转移结节。2016年6月,他在组织病理学上被诊断为ALK阳性cT4N0M1a腺癌。肿瘤的NGS鉴定为罕见的LOC388942-ALK融合(L基因间:A20,1.41%)。然后,病人接受了化疗,克唑替尼,ceritinib,阿列替尼,和安洛替尼顺序。患者对化疗和克唑替尼达到部分反应(PR)。在克唑替尼后没有发现继发性耐药分子事件的证据,ceritinib,或者阿莱替尼。阿来替尼治疗8个月后,肿瘤又逐渐增大。Anlotinib随访13个月。十三个月后,右肺下叶出现新的病变,并逐渐增加,表明肿瘤的明确进展。使用cfDNANGS检测经典ALKG1202R抗性突变。患者拒绝接受以G1202R耐药突变为目标的氯拉替尼,继续使用安洛替尼。他于2022年8月死亡,实现了5年的总体生存(OS)。
未经证实:NSCLC中不同的ALK融合具有不同的癌症生物学特性,导致对ALK酪氨酸激酶抑制剂(ALK-TKIs)的不同反应,甚至发展了不同的抗性机制。报道NSCLC中罕见ALK融合的临床细节对于指导临床医生和研究人员的治疗是必要的。
UNASSIGNED: Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is a heterogeneous disease. To date, more than ninety ALK fusions in lung cancer have been found. Here, we report for the first time a rare LOC388942-ALK fusion in NSCLC was sensitive to crizotinib but resistant to the sequential ceritinib and alectinib and acquired classical ALK G1202R resistance mutation after long-term treatment with anlotinib. This
case highlights dynamic monitoring of gene alteration using next-generation sequencing (NGS) is necessary during the anti-tumor process.
UNASSIGNED: A 55-year-old male, with no history of smoking history and no family history of cancer, was found malignant pleural effusion and multiple metastasis nodules in the left lung. He was histopathologically diagnosed with ALK-positive cT4N0M1a adenocarcinoma in June 2016. NGS of the tumor identified a rare LOC388942-ALK fusion (L intergenic: A 20, 1.41%). Then, the patient was treated with chemotherapy, crizotinib, ceritinib, alectinib, and anlotinib sequentially. The patient achieved partial response (PR) to chemotherapy and crizotinib. No evidence of a secondary resistant molecular event was found after resistance to crizotinib, ceritinib, or Alectinib. After 8 months of alectinib treatment, the tumor gradually enlarged again. Anlotinib was followed for 13 months. Thirteen months later, new lesions in the lower lobe of the right lung appeared and increased gradually, indicating definite progression of the tumor. Classical ALK G1202R resistance mutations was detected using cfDNA NGS. The patient refused to receive lorlatinib targeting G1202R resistance mutations and continued with anlotinib. He dead in August 2022, achieving 5-year overall survival (OS).
UNASSIGNED: Distinct ALK fusions in NSCLC have different cancer biology, leading to different response to ALK tyrosine kinase inhibitors (ALK-TKIs), even developed different resistance mechanism. Reporting the clinical details of rare ALK fusions in NSCLC is necessary to guide the treatment for clinicians and researchers.