Jin Feng, Wang Chenyang, Yang Fang, Wang Shubin, Wang Fen
Department of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen, China.
Shenzhen University, Shenzhen, China.
Front Genet. 2025 Jun 17;16:1569912. doi: 10.3389/fgene.2025.1569912. eCollection 2025.
Anaplastic lymphoma kinase () fusion, an oncogenic driver alteration, accounts for 5%-6% of non-small cell lung cancer (NSCLC) patients. tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in advanced ALK-rearranged NSCLC. However, acquired resistance to TKIs inevitably arises, and the underlying mechanisms remain incompletely elucidated. This report describes a stage IV lung adenocarcinoma (LUAD) patient with -rearranged who developed fusion-mediated resistance following second-line alectinib therapy. The patient achieved a partial response (PR) to third-line pralsetinib, sustained for 4 months. This case highlights fusion as a potential resistance mechanism post alectinib treatment and suggested = pralsetinib, a inhibitor, as a viable therapeutic option in this context. These findings contribute to the evolving understanding of resistance management strategies in -rearranged NSCLC.
间变性淋巴瘤激酶（ALK）融合是一种致癌驱动改变，在非小细胞肺癌（NSCLC）患者中占5%-6%。ALK酪氨酸激酶抑制剂（TKIs）在晚期ALK重排的NSCLC中提供显著的临床益处。然而，对ALK TKIs的获得性耐药不可避免地出现，其潜在机制仍未完全阐明。本报告描述了一名IV期肺腺癌（LUAD）患者，其ALK重排，在二线阿来替尼治疗后出现了EML4-ALK融合介导的耐药。该患者对三线普拉替尼获得了部分缓解（PR），持续了4个月。本病例突出了EML4-ALK融合作为阿来替尼治疗后潜在的耐药机制，并提示在这种情况下，ALK抑制剂普拉替尼是一种可行的治疗选择。这些发现有助于不断发展对ALK重排NSCLC耐药管理策略的理解。
