Wdowiak Krystian, Dolar-Szczasny Joanna, Rejdak Robert, Drab Agnieszka, Maciocha Agnieszka
University Clinical Hospital No. 4 in Lublin, K. Jaczewskiego 8 St., 20-954 Lublin, Poland.
Department of General and Pediatric Ophthalmology, Medical University of Lublin, 20-093 Lublin, Poland.
J Clin Med. 2025 Jun 8;14(12):4058. doi: 10.3390/jcm14124058.
: Uveal melanoma (UM) is a relatively rare malignancy, yet it remains the most common primary intraocular cancer in adults. Several risk factors have been identified, including light iris color, fair skin tone, and cutaneous freckles. : The aim of this article was an overview of the treatment methods for uveal melanoma, with a particular focus on emerging therapies such as tebentafusp and da-rovasertib. The research method was a review of the latest literature. : Genetic studies have uncovered key mutations in and , which significantly contribute to UM pathogenesis. Treatment selection depends on tumor location and disease stage. In localized disease, radiotherapy-especially brachytherapy-is commonly used and generally effective. However, the prognosis worsens significantly once distant metastases, most often to the liver, develop, as no standard systemic therapy has demonstrated high efficacy in this setting. Recent years have seen the emergence of promising therapies, including tebentafusp, which stimulates immune responses against gp100-expressing melanoma cells, and darovasertib, a potent PKC inhibitor that targets MAPK pathway activation driven by / mutations. Both agents have shown encouraging tolerability; tebentafusp has demonstrated clinical benefit in Phase II and III trials, while darovasertib is still under investigation. Additionally, melphalan-based liver-directed therapy, particularly via hepatic arterial infusion (approved by the FDA), has shown potential in controlling liver-dominant disease in metastatic UM. This localized approach may provide significant benefit for patients with limited extrahepatic spread. : Future research should focus on optimizing these novel strategies-tebentafusp, darovasertib, melphalan, and combination therapies-and on expanding our understanding of UM's molecular drivers to enable the development of more effective, personalized treatments.
葡萄膜黑色素瘤（UM）是一种相对罕见的恶性肿瘤，但仍是成人中最常见的原发性眼内癌。已确定了几个风险因素，包括浅虹膜颜色、白皙肤色和皮肤雀斑。本文旨在概述葡萄膜黑色素瘤的治疗方法，特别关注如替贝福司和达罗伐塞替布等新兴疗法。研究方法是对最新文献进行综述。基因研究发现了 和 中的关键突变，这些突变对UM的发病机制有显著影响。治疗方案的选择取决于肿瘤位置和疾病分期。在局限性疾病中，放疗尤其是近距离放疗常用且通常有效。然而，一旦发生远处转移（最常见的是转移至肝脏），预后会显著恶化，因为在此情况下尚无标准的全身治疗显示出高效。近年来出现了一些有前景的疗法，包括刺激针对表达gp100的黑色素瘤细胞的免疫反应的替贝福司，以及靶向由 / 突变驱动的MAPK途径激活的强效PKC抑制剂达罗伐塞替布。两种药物都显示出令人鼓舞的耐受性；替贝福司在II期和III期试验中已显示出临床益处，而达罗伐塞替布仍在研究中。此外，基于美法仑的肝脏定向治疗，特别是通过肝动脉灌注（已获美国食品药品监督管理局批准），在控制转移性UM中以肝脏为主的疾病方面已显示出潜力。这种局部治疗方法可能为肝外扩散有限的患者带来显著益处。未来的研究应专注于优化这些新策略——替贝福司、达罗伐塞替布、美法仑和联合疗法——并扩大我们对UM分子驱动因素的理解，以开发更有效且个性化的治疗方法。
