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REVIEW

Clinical Molecular Pathology and Treatment Developments in Advanced Uveal Melanoma: State of the Art

Stefano Dore1, Matteo Sachi1, Antonio Pinna1, Giuseppe Palmieri2,3, Panagiotis Paliogiannis4,*
1 Unit of Ophthalmology, Department of Medicine, Surgery and Pharmacy, University of Sassari, Viale San Pietro 43, Sassari, 07100, Italy
2 Unit of Cancer Genetics, Institute of Genetic & Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca n. 3, Sassari, 07100, Italy
3 Immuno-Oncology & Targeted Cancer Biotherapies, University Hospital (AOU) of Sassari, Viale San Pietro 43, Sassari, 07100, Italy
4 Anatomic Pathology and Histology, University Hospital (AOU) of Sassari, Via Matteotti 60, Sassari, 07100, Italy
* Corresponding Author: Panagiotis Paliogiannis. Email: email

Oncology Research https://doi.org/10.32604/or.2025.071831

Received 13 August 2025; Accepted 17 December 2025; Published online 04 January 2026

Abstract

Uveal melanoma (UM) is the most common intraocular cancer, with approximately 5.2 individuals per million affected annually in the United States. It represents approximately 3% of the global malignant melanoma cases, accounting for 80% of the overall noncutaneous melanomas. Clinically, it remains silent in about 30% of the cases; when symptomatic, it generally causes metamorphopsia (painless loss or distortion of vision) and/or photopsia (flashing or flickering of light in the visual field). Discoloration of the iris, astigmatism, glaucoma, and even blindness are other, less common clinical manifestations. Several pathophysiological mechanisms underlie the development of UM. Genetic mutations, involving especially the G protein subunit alpha q (GNAQ), guanine nucleotide-binding protein subunit alpha-11 (GNA11), BRCA1 associated deubiquitinase 1 (BAP1), splicing factor 3b subunit 1 (SF3B1), and eukaryotic translation initiation factor 1A, X-linked (EIF1AX) genes as well as the MAPK/ERK signaling pathway genes, have been largely associated with the development of UM. Chromosomal aberrations, inflammatory and immunological alterations are often concurrent factors for the development and progression of UM. Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs. This review aims to present the latest advances in the clinical molecular pathology of UM, along with the resulting targeted, immunological, and other therapies that have been introduced or are currently under investigation.

Keywords

Eye; uveal melanoma (UM); molecular pathology; targeted therapy; immunotherapy

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