抑制脉管畸形的相关靶向药物研究进展  

Research progress on targeted drugs for vascular malformations

作　　者：沈禹辰 王德明[1] 范新东[1] SHEN Yuchen;WANG Deming;FAN Xin-dong(Department of Interventional Therapy,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China.)

机构地区：[1]上海交通大学医学院附属第九人民医院介入科,上海200011

出　　处：《口腔疾病防治》2023年第4期284-289,共6页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金(81871458)。

摘　　要：脉管畸形是一种先天性疾患,主要发生在头颈部,其无法自行消退,且随着患者的生长而逐渐加重。脉管畸形的传统治疗方式包括:激光治疗、硬化治疗、介入栓塞、手术切除等。但是对于一些范围较大的病变,传统治疗方式效果不佳。随着分子遗传学的发展,基因突变目前被认为是脉管畸形发生的根本原因,基因突变引起的相关通路的活化进一步促进了脉管畸形病变的进展。低流速脉管畸形主要涉及磷脂酰肌醇3⁃激酶(phosphatidylinositol 3⁃kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)通路的激活;而高流速的脉管畸形主要涉及大鼠肉瘤(rat sarcoma,RAS)/快速加速纤维肉瘤(rapidly accelerated fibrosarcoma,RAF)/促分裂原活化蛋白激酶激酶(mitogen⁃activated protein kinase kinase,MAPKK)/细胞外信号调节激酶(extracellular⁃signalregulated protein kinase,ERK)通路的激活。目前,针对相关基因突变及信号通路的靶向药物也逐渐应用到脉管畸形的治疗中。mTOR抑制剂——雷帕霉素被广泛应用于低流速脉管畸形的靶向治疗;PI3K抑制剂——阿培利司在静脉畸形的治疗中也具有良好的前景;MAPKK抑制剂——曲美替尼在动静脉畸形的治疗中取得了良好的疗效。因此,传统治疗辅以靶向药物的方式或为脉管畸形治疗带来新的突破。Vascular malformations, which mainly occur in the head and neck region, are a group of congenital disorders that cannot involute and dilate gradually as patients grow. Traditional therapeutic strategies for vascular malformations include laser therapy, sclerotherapy, interventional embolization, surgical resection, etc. However, for some cases with a relatively larger range of lesions, traditional therapeutic strategies might fall short of the goals. With the development of molecular genetics, gene mutations are currently recognized as the root cause of the occurrence of vascular malformations. The progression of vascular malformation lesions is further promoted by the activation of related pathways.Low-flow vascular malformations mainly involve activation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) pathway, whereas high-flow vascular malformations mainly involve activation of the rat sarcoma(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase kinase(MAPKK)/extracellular-signal regulated protein kinase(ERK) pathway. Targeted drugs against relevant gene mutations and signaling pathways have also been applied in the treatment of vascular malformations, and previous studies have shown that the m TOR inhibitor rapamycin is effective and now widely used in the treatment of low-flow vascular malformations. The PI3K inhibitor alpelisib is also promising in the treatment of venous malformations, and the MAPKK inhibitor trametinib has shown good results in the treatment of arteriovenous malformations. Therefore, traditional therapies supplemented by targeted drugs may bring new breakthroughs to the treatment of vascular malformations.

关 键 词：脉管畸形 信号通路 哺乳动物雷帕霉素靶蛋白复合物⁃1 促分裂原活化蛋白激酶激酶 雷帕霉素 曲美替尼 血管内皮生长因子 

分 类 号：R78[医药卫生—口腔医学]