A Brief Overview of Uveal Melanoma Treatment Methods with a Focus on the Latest Advances

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: Genetic studies have uncovered key mutations in <i>GNAQ</i> and <i>GNA11</i>, 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 <i>GNAQ</i>/<i>GNA11</i> 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. <b>Conclusions</b>: 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.

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Publication Details

Journal
Journal of Clinical Medicine
Published
2025-06-08
DOI
https://doi.org/10.3390/jcm14124058
Citations
4
Primary Topic
Ocular Oncology and Treatments
Type
article
Field-Weighted Citation Impact
6.83
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article

A Brief Overview of Uveal Melanoma Treatment Methods with a Focus on the Latest Advances

Robert Ręjdak, Krystian Wdowiak, Agnieszka Barańska, Joanna Dolar-Szczasny et al.
4 citations
Journal of Clinical Medicine
Ocular Oncology and Treatments
6.83
article

A Brief Overview of Uveal Melanoma Treatment Methods with a Focus on the Latest Advances

Robert Ręjdak, Krystian Wdowiak, Agnieszka Barańska, Joanna Dolar-Szczasny, Agnieszka Maciocha
article en
4 citations

Abstract

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: Genetic studies have uncovered key mutations in <i>GNAQ</i> and <i>GNA11</i>, 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 <i>GNAQ</i>/<i>GNA11</i> 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. <b>Conclusions</b>: 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.

Journal of Clinical MedicineVol. 14(12)
Medical University of Lublin (PL), 1 Military Clinical Hospital with Outpatient Clinic (PL)
Openalex Percentile: Top 3%
Ocular Oncology and Treatments
6.83
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