葡萄膜黑色素瘤的治疗进展:靶向GNAQ/11驱动突变  

Emerging Therapeutic Strategies for Metastatic Uveal Melanoma:Targeting GNAQ/11 Driver Mutations

作　　者：张贵明 刘小莲 李亦蕾 余乐[2] ZHANG Guiming;LIU Xiaolian;LI Yilei;YU Le(Clinical Pharmacy Center,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China;Innovative Group in Drug Design and Discovery Research,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,Guangdong 510515,China)

机构地区：[1]南方医院临床药学中心,广东广州510515 [2]南方医科大学药学院药物设计与发现研究创新群体,广东广州510515

出　　处：《今日药学》2025年第1期74-80,共7页Pharmacy Today

基　　金：广东省药学会研究基金(2022ZX02,2022ZX05);吴阶平医学基金会临床科研专项(320.6750.2024-6-51)。

摘　　要：葡萄膜黑色素瘤(uveal melanoma)是成人眼内最常见的原发性恶性肿瘤,虽然其可以得到有效控制,但相当一部分病例(超过40%)最终会发生远处转移。转移性葡萄膜黑色素瘤仍是一种致死性疾病,但治疗手段和药物有限,且以原癌基因GNAQ或其旁系同源基因GNA11高频突变为特征。GNAQ/11突变后激活多条信号通路,主要包括PKC/MAPK,PI3K/AKT/mTOR和Hippo/YAP等。本文综述了GNAQ/11突变激活的主要信号通路,重点讨论了针对以上信号通路的新兴的靶向治疗药物和策略,并介绍了正在进行的临床试验的药物。Uveal melanoma(UM) is the most common primary malignant intraocular tumor in adults.Although primary UM can be effectively controlled,a significant proportion of cases(40% or more) eventually develop distant metastases,commonly in the liver.Metastatic UM remains a lethal disease with limited treatment options.The initiation of UM is typically characterized by high-frequency oncogenic mutations in GNAQ or GNA11.The elucidation of the downstream pathways such as PKC/MAPK,PI3K/AKT/mTOR,and Hippo/YAP has provided potential therapeutic targets.This review introduced the major signaling pathways activated by oncogenic GNAQ/11 mutations and focuses on emerging targeted therapeutic drugs and strategies for these pathways,as well as the drugs in ongoing clinical trials.

关 键 词：葡萄膜黑色素瘤 GNAQ/11突变 靶向治疗 临床试验 

分 类 号：R739.7[医药卫生—肿瘤]