Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations

Liu, Xiao-lian1,2; Run-hua, Zhou2; Pan, Jing-xuan3; Li, Zhi-jie4,5; Yu, Le2; Li, Yi-lei1

2024-05-01

10.1111/pcmr.13161

PIGMENT CELL & MELANOMA RESEARCH   影响因子和分区

1755-1471

1755-148X

["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 attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo-YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.","In this review, we provide an overview of the emerging targeted and epigenetic therapeutic strategies for metastatic uveal melanoma harbouring specific driver mutations, which include GNAQ/11, BAP1 and SF3B1. Furthermore, we highlight the upcoming or ongoing clinical trials regarding these therapeutic strategies.image"]

clinical trials driver mutations epigenetic therapy immunotherapy targeted therapy uveal melanoma

SCI

英语

通讯

Guangdong Basic and Applied Basic Research Foundation["2022A1515011824","2023A1515010401"] ; Open Research Funds of the State Key Laboratory of Ophthalmology[2022KF06] ; GuangDong Pharmaceutical Association Research Grant["2022ZX02","2022ZX05"] ; null[82373959] ; null[81973357]

Oncology ; Cell Biology ; Dermatology

Oncology ; Cell Biology ; Dermatology

WOS:001173593500001

WILEY

Web of Science

1.Southern Med Univ, Nanfang Hosp, Dept Pharm, Guangzhou 510515, Peoples R China
2.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China
3.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China
4.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Shenzhen 518020, Peoples R China
5.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Peoples R China

Liu, Xiao-lian,Run-hua, Zhou,Pan, Jing-xuan,et al. Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations[J]. PIGMENT CELL & MELANOMA RESEARCH,2024,37(3).

Liu, Xiao-lian,Run-hua, Zhou,Pan, Jing-xuan,Li, Zhi-jie,Yu, Le,&Li, Yi-lei.(2024).Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations.PIGMENT CELL & MELANOMA RESEARCH,37(3).

Liu, Xiao-lian,et al."Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations".PIGMENT CELL & MELANOMA RESEARCH 37.3(2024).