SLC8A1-ALK融合突变晚期肺腺癌1例及文献复习

Advanced Lung Adenocarcinoma Harboring SLC8A1-ALK Fusion: A Case Report and Literature Review

摘要: ALK融合基因多样，通常发生在基因组第20外显子的共同断点，目前已发现的ALK融合基因约有90多种。NSCLC中最常见的ALK融合基因是EML4-ALK，ALK-TKI药物治疗有效。然而，不同ALK融合类型的患者对不同ALK-TKI药物的治疗反应存在差异。SLC8A1-ALK是一种罕见的融合基因，由SLC8A1基因的第2外显子与ALK基因的第20外显子重排而成，对ALK-TKIs反应的临床数据尚不全面。本研究报告了一例晚期肺腺癌患者，其最初携带EML4-ALK融合，在接受伊鲁阿克治疗并发生耐药后，检测出新出现的SLC8A1-ALK融合，且对洛拉替尼治疗也产生了耐药并出现疾病进展。鉴于ALK融合基因的多样性以及ALK-TKIs的不同疗效，我们认为本病例报告具有重要的临床参考价值，旨在为晚期NSCLC的靶向治疗提供新的参考。

Abstract: ALK fusion genes exhibit substantial diversity, with a conserved breakpoint typically localized to exon 20 of the genome. To date, more than 90 distinct ALK fusion variants have been identified. In non-small cell lung cancer (NSCLC), the EML4-ALK fusion represents the most prevalent subtype, which shows favorable responsiveness to treatment with ALK tyrosine kinase inhibitor (ALK-TKI) agents. Nevertheless, patients harboring different ALK fusion subtypes display varying treatment responses to distinct ALK-TKIs. SLC8A1-ALK is a rare fusion oncogene, arising from the rearrangement between exon 2 of the SLC8A1 gene and exon 20 of the ALK gene. Clinical evidence regarding its responsiveness to ALK-TKIs remains limited and incomplete. This study reports a case of a patient with advanced lung adenocarcinoma who was initially positive for the EML4-ALK fusion. Following the development of acquired resistance to Iruplinalkib treatment, an emergent SLC8A1-ALK fusion was detected. Eventually, the patient also developed resistance to Lorlatinib treatment, accompanied by progressive disease. Given the inherent diversity of ALK fusion genes and the variable efficacy profiles of different ALK-TKIs, we conclude that this case report holds significant clinical reference value, aiming to provide novel insights for the targeted therapy of advanced NSCLC.