Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma.
Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma.
复制标题
DOI：
10.1158/1541-7786.mcr-17-0007
复制
发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Aplin AE
中科院分区：
文献类型：
--
作者：
Chua V;Lapadula D;Randolph C;Benovic JL;Wedegaertner PB;Aplin AE
葡萄膜黑色素瘤(UM)是成人最常见的原发眼内恶性肿瘤，起源于葡萄膜区黑素细胞的转化。即使在原发肿瘤治疗后，也有高达50%的患者死于转移性疾病。肝脏是主要的转移器官。有必要为晚期UM提供有效的治疗选择。为了为新的治疗提供临床前基础，了解该病的分子基础是很重要的。最近的基因组研究表明，G蛋白偶联受体(GPCR)信号组件内的突变是约98%的UM相关的早期事件。这篇综述讨论了GPCR信号组分(GNAQ和GNA11)的变化、失调的GPCR信号级联以及可行的靶向治疗，旨在为UM的新治疗策略提供洞察力。
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage UM. In order to provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease. Recent genomic studies have shown that mutations within components of G protein-coupled receptor (GPCR) signaling are early events associated with ~98% of UMs. This review discusses the alterations in GPCR signaling components (GNAQ and GNA11), dysregulated GPCR signaling cascades, and viable targeted therapies with the intent to provide insight into new therapeutic strategies in UM.