Study of Gq mutations and their inhibitors in uveal melanoma
10.16438/j.0513-4870.2020-0743
- VernacularTitle:Gq突变在葡萄膜黑色素瘤中的作用及其抑制剂研究进展
- Author:
Shuo SHI
1
;
Kai ZHU
2
;
Xiao-feng XIONG
1
;
Xiao-lei ZHANG
1
Author Information
1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
2. Changchun University of Chinese Medicine, Changchun 130117, China
- Publication Type:Research Article
- Keywords:
uveal melanoma;
G protein;
GNAQ/GNA11;
G protein-coupled receptor;
small molecule
- From:
Acta Pharmaceutica Sinica
2020;55(7):1382-1392
- CountryChina
- Language:Chinese
-
Abstract:
Uveal melanoma (UM) is one of most common ocular cancers and is extremely malignant; so far there is no effective treatment. Moreover, the survival period is only 2-7 months after metastasis. It has been proven that more than 83% of uveal melanomas harbor mutations in G protein subunit α q (GNAQ) or G protein subunit α 11 (GNA11), among which 95% are a Q209P/L single-site mutation. Q209P/L mutations lead to dysfunction of guanine triphosphatase (GTPase) in the G protein and result in constitutive activation of downstream pathways including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), Ras homologue (Rho)/ Rho-associated kinase (Rock)/Yes-associated protein (YAP) and others. Therefore, targeting GNAQ/GNA11 mutations are potential strategies for UM treatment. This review will focus on roles of G protein mutations in UM progression, and the potential therapeutic effects of GNAQ/GNA11 inhibitors, and will provide insights into basic and clinical research on UM treatment.
