McAvoy Malia, Ratner Buddy, Ferreira Manuel J, Levitt Michael R
Neurological Surgery, University of Washington, Seattle, Washington, USA.
Chemical Engineering, Bioengineering, Materials Science, and Engineering, University of Washington, Seattle, Washington, USA.
J Neurointerv Surg. 2025 Jul 14;17(8):859-863. doi: 10.1136/jnis-2024-021843.
Treatment of intracranial aneurysms is currently limited to invasive surgical and endovascular modalities, and some aneurysms are not treatable with these methods. Identification and targeting of specific molecular pathways involved in the pathogenesis of aneurysms may improve outcomes. Low frequency somatic variants found in cancer related genes have been linked to intracranial aneurysm development. In particular, mutations in the gene lead to constitutively activated ERK and nuclear factor κB signaling pathways, which can be targeted with tyrosine kinase inhibitors. In this review, we describe how low frequency somatic variants in oncogenic and other genes affect the pathogenesis of aneurysm development, with a focus on gene therapy applications, such as endovascular in situ delivery of chemotherapeutics.
颅内动脉瘤的治疗目前仅限于侵入性手术和血管内治疗方式，并且有些动脉瘤无法用这些方法治疗。识别和靶向参与动脉瘤发病机制的特定分子途径可能会改善治疗效果。在癌症相关基因中发现的低频体细胞变异与颅内动脉瘤的发生有关。特别是，该基因的突变会导致ERK和核因子κB信号通路持续激活，而酪氨酸激酶抑制剂可以靶向这些通路。在这篇综述中，我们描述了致癌基因和其他基因中的低频体细胞变异如何影响动脉瘤发展的发病机制，重点关注基因治疗应用，如血管内原位递送化疗药物。
