颅外动静脉畸形的遗传学与靶向治疗研究进展

Advancement of genetics and target therapy of extracranial arteriovenous malformation

颅外动静脉畸形(arteriovenous malformation,AVM)作为一种高流量脉管畸形,目前以手术和无水乙醇介入为主的治疗风险较高,且复杂颅外AVM的预后不佳。因此,在遗传学和病理机制的研究基础上加速靶向治疗的研究是该领域的当务之急。近年来颅外AVM的遗传学研究突破性地发现了该疾病存在RAS/RAF/MAPK通路相关基因的体细胞突变,基因多态性和表观遗传学可能在病理机制中同样具有潜在价值。目前多种抗血管生成治疗显示对颅外AVM可能存在治疗作用,另一方面高通量蛋白组学为颅外AVM的精准治疗提供了新的思路。该文从以上几个方面对近期颅外AVM相关的病理机制、遗传学和靶向治疗的研究进展进行了综述。

Extracranial arteriovenous malformation(AVM)is a high-flow vascular malformation,of which the first-line therapies including surgery and ethanol embolization are of high risk.Besides,the outcomes of complex cases are usually poor.Therefore,it is urgent to accelerate the development of target therapy for extracranial AVM,based on the discoveries in pathogenesis and genetics.Breakthroughs have been made on the genetic research of extracranial AVM,as somatic mutations of RAS/RAF/MAPK signaling pathway genes have been found in this entity.Genetic polymorphism and epigenetics might also play important role in the development of the disease.Several anti-angiogenic treatment emerge therapeutic effects on extracranial AVM,meanwhile high-throughput proteomics ignites the sparks of precision medicine.This review focuses on the advancement in the pathogenesis,genetics and target therapy related to extracranial arteriovenous malformations.