Gupta Brinda, Borghaei Leila, Liu Stephen V
Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC, 20007, USA.
University of Virginia, Charlottesville, VA, USA.
Curr Oncol Rep. 2025 Feb;27(2):190-194. doi: 10.1007/s11912-025-01640-y. Epub 2025 Jan 31.
Neuregulin 1 (NRG1) fusions are rare but actionable oncogenic drivers that occur in a variety of tumor types, including non-small cell lung cancer (NSCLC). These fusions lead to pathophysiologic activation of HER signaling pathways, promoting tumor growth, invasion, and metastasis. Current evidence suggests that NRG1 fusion-positive NSCLC does not respond well to conventional treatments such as immunotherapy and chemotherapy. This review focuses on the biology and detection of NRG1 fusions and the evolving therapeutic landscape of NSCLC harboring NRG1 fusions.
Zenocutuzumab, a bispecific antibody targeting HER2 and HER3, is the first FDA approved treatment for previously treated NRG1 fusion-positive NSCLC and pancreatic cancer. Additional NRG1 fusion directed strategies are in development. NRG1 fusions are rare molecular drivers of NSCLC that can be effectively treated with targeted therapies. Here, we summarize the biology and detection of NRG1 fusions, the currently approved bispecific antibody used to treat NRG1 fusion-positive NSCLC, and new agents under investigation.
神经调节蛋白1（NRG1）融合是罕见但可靶向治疗的致癌驱动因素，存在于多种肿瘤类型中，包括非小细胞肺癌（NSCLC）。这些融合导致HER信号通路的病理生理激活，促进肿瘤生长、侵袭和转移。目前的证据表明，NRG1融合阳性的NSCLC对免疫疗法和化疗等传统治疗反应不佳。本综述重点关注NRG1融合的生物学特性、检测方法以及携带NRG1融合的NSCLC不断演变的治疗前景。
泽诺库izumab是一种靶向HER2和HER3的双特异性抗体，是首个获得美国食品药品监督管理局（FDA）批准用于治疗既往接受过治疗的NRG1融合阳性NSCLC和胰腺癌的药物。其他针对NRG1融合的治疗策略正在研发中。NRG1融合是NSCLC罕见的分子驱动因素，可通过靶向治疗有效治疗。在此，我们总结了NRG1融合的生物学特性和检测方法、目前批准用于治疗NRG1融合阳性NSCLC的双特异性抗体以及正在研究的新药物。
