1型神经纤维瘤病发病机制及治疗进展

Pathogenesis and Therapeutic Advances of Neurofibro-matosis Type 1

1型神经纤维瘤病(neurofibromatosis type 1,NF1)是一种常见的遗传性神经皮肤综合征,发病率为1/3500,主要表现为皮肤、神经、骨骼等多个系统的肿瘤形成。NF1基因突变导致神经纤维蛋白功能丧失,受神经纤维蛋白负调控的Ras信号失去抑制,导致MAPK信号通路组成型激活,该信号通路的异常激活与肿瘤微环境等机制促使NF1肿瘤发生。目前,主流的治疗方式包括针对Raf/MEK/ERK通路和/或mTOR通路的靶向抑制剂。近年来,对NF1的遗传学、临床特征、肿瘤起源、异常信号通路以及相关靶向抑制剂的疗效等方面的研究日益增多。深入了解NF1的病理生物学和分子机制将为开发更有效的靶向治疗方法提供坚实的基础。

Neurofibromatosis type 1(NF1)is a prevalent hereditary neurocutaneous syndrome with a prevalence of 1/3500,It was characterized by the formation of tumors with affecting the skin,nerves,bones,and multiple systems.Mutations in the NF1 gene lead to the loss of neurofibrillary protein function and the loss of inhibition of Ras signaling,which is negatively regulated by neurofibrillary protein,leading to the persistent activation of downstream signaling,and the combination of the abnormal activation of this pathway and the tumor microenvironment contributes to NF1 tumorigenesis.Current therapeutic approaches for NF1 mainly involve targeted inhibitors against the Raf/MEK/ERK pathway and/or the mTOR pathway.Many researchers are increasingly focusing on the genetics,clinical features,tumor origins,aberrant signaling pathways and efficacy of relevant targeted inhibitors for NF1.Further study of the pathobiology and molecular mechanisms of NF1 may provide a solid foundation for the development of more effective targeted therapies.