NRG1 基因融合——这些罕见的基因改变背后还有什么希望？生物学、诊断方法和临床意义的综合综述。
NRG1 Gene Fusions-What Promise Remains Behind These Rare Genetic Alterations? A Comprehensive Review of Biology, Diagnostic Approaches, and Clinical Implications.
发表日期：2024 Aug 05
作者：
Tomasz Kucharczyk, Marcin Nicoś, Marek Kucharczyk, Ewa Kalinka
来源：
Cancers
摘要：
非小细胞肺癌（NSCLC）呈现出多种可药物治疗的基因改变，彻底改变了治疗方法。然而，识别新的改变可能会扩大受益于此类新治疗方案的患者群体。最近，人们的兴趣集中在神经调节蛋白-1 基因 (NRG1) 上，该基因的融合可能已成为潜在的预测因素。迄今为止，NRG1融合的发生被认为是NSCLC治疗中的阴性预后标志物。然而，受 NRG1 基因影响的信号通路的靶向性仍然存在许多前提。 NRG1 融合在 ErbB 介导的细胞增殖中的作用尤其被认为是治疗的主要目标。因此，携带 NRG1 融合的 NSCLC 患者可能会受益于靶向治疗，例如泛 HER 家族抑制剂和抗 HER 单克隆抗体，该抑制剂在之前的研究中已在多种癌症中显示出疗效。考虑到人们对 NRG1 基因作为潜在临床靶点的兴趣日益浓厚，在下面的综述中，我们重点介绍了其生物学，以及在临床中评估或在临床试验中仍在考虑的潜在临床意义。
Non-small cell lung cancer (NSCLC) presents a variety of druggable genetic alterations that revolutionized the treatment approaches. However, identifying new alterations may broaden the group of patients benefitting from such novel treatment options. Recently, the interest focused on the neuregulin-1 gene (NRG1), whose fusions may have become a potential predictive factor. To date, the occurrence of NRG1 fusions has been considered a negative prognostic marker in NSCLC treatment; however, many premises remain behind the targetability of signaling pathways affected by the NRG1 gene. The role of NRG1 fusions in ErbB-mediated cell proliferation especially seems to be considered as a main target of treatment. Hence, NSCLC patients harboring NRG1 fusions may benefit from targeted therapies such as pan-HER family inhibitors, which have shown efficacy in previous studies in various cancers, and anti-HER monoclonal antibodies. Considering the increased interest in the NRG1 gene as a potential clinical target, in the following review, we highlight its biology, as well as the potential clinical implications that were evaluated in clinics or remained under consideration in clinical trials.