Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations

IF 3.9 3区 医学 Q2 CELL BIOLOGY Pigment Cell & Melanoma Research Pub Date : 2024-02-27 DOI:10.1111/pcmr.13161
Xiao-lian Liu, Zhou Run-hua, Jing-xuan Pan, Zhi-jie Li, Le Yu, Yi-lei Li
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Abstract

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.

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转移性葡萄膜黑色素瘤的新兴治疗策略:靶向驱动突变。
葡萄膜黑色素瘤(UM)是成人最常见的原发性眼内恶性肿瘤。虽然原发性 UM 可以得到有效控制,但很大一部分病例(40% 或更多)最终会发生远处转移,常见于肝脏。转移性 UM 仍是一种致命疾病,治疗方案有限。UM 的发生通常归因于 GNAQ 或 GNA11 的激活突变。对 PKC/MAPK、PI3K/AKT/mTOR 和 Hippo-YAP 等下游通路的阐明提供了潜在的治疗靶点。BRCA1 相关蛋白 1(BAP1)或剪接因子 3b 亚基 1(SF3B1)的并发突变被认为是获得恶性潜能的关键。此外,在临床前研究中,已经发现了与 BAP1 缺失或致癌突变 SF3B1 相关的可操作靶点,为 UM 治疗提供了有希望的途径。本综述旨在总结针对携带特定驱动基因突变的转移性 UM 的新兴靶向和表观遗传学治疗策略,以及将这些方法与免疫疗法相结合的潜力,并特别关注那些即将或正在进行的临床试验。
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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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