Current Treatment of Uveal Melanoma
Simple Summary
Abstract
1. Introduction
2. Uveal Melanoma
2.1. Overview: Prognosis
2.2. Current Treatments
2.2.1. Treatment of Primary Uveal Melanoma
2.2.2. Treatment of Metastatic Uveal Melanoma
3. Current Immunotherapies in mUM
3.1. Immune Checkpoint Inhibitor Therapy
3.1.1. CTLA-4
3.1.2. PD-1 and PDL-1 Inhibitors
3.2. T-Cell Direction Therapy
3.3. Clinical Trials
4. Future Directions
4.1. Selective Biomarkers: Patient Stratification
4.2. Multimodal Therapies
4.3. Emerging Targeted Therapies
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
APC | Antigen-Presenting Cell |
ATP | Adenosine TriPhosphate |
BAP1 | BRCA1-associated protein 1 |
BiTE | Bispecific T-cell Engager |
CD | Cluster of Differentiation |
c-MET | c-Mesenchymal-Epithelial Transition Factor |
CT | Computerised Tomography |
CTLA-4 | Cytotoxic T-Lymphocyte Associated Protein 4 |
CYSLTR2 | Cysteinyl Leukotriene Receptor 2 |
CXCL | Chemokine (C-X-C motif) Ligand |
CXCR3 | C-X-C Chemokine Receptor 3 |
EIF1AX | Initiation Factor 1A X-linked |
FDA | Food and Drug Administration |
FNA | Fine Needle Aspiration |
GAGs | Glycosaminoglycans |
GNA11 | Guanosine Nucleotide-Binding Protein Alpha-11 |
GNAQ | Guanosine Nucleotide-Binding Protein Alpha-Q Gene |
gp100 | Glycoprotein 100 |
HDAC | Histone Deacetylase |
HLA | Human Leukocyte Antigen |
HR | Hazard Ratio |
ICI | Immune Checkpoint Inhibitor |
IV | Intravenous |
LAG3 | Lymphocyte Activation Gene 3 |
mAb | Monoclonal Antibody |
MBD4 | Methyl-CpG Binding Domain Protein 4 |
MEK | Mitogen-Activated Extracellular Signal-Regulated Kinase |
MET | Mesenchymal-Epithelial Transition Factor |
MHC | Major Histocompatibility Complex |
MRI | Magnetic Resonance Imaging |
MS | Median Survival |
mTKI | Multitargeted Tyrosine Kinase Inhibitors |
mUM | Metastatic Uveal Melanoma |
OS | Overall Survival |
PD-1 | Programmed Cell Death Protein 1 |
PD-L1 | Programmed Death-Ligand 1 |
PHP | Percutaneous Hepatic Perfusion |
PI3K | Phosphoinositide 3-Kinase |
PI3Kδ | Phosphoinositide 3-kinase delta |
PKC | Protein Kinase C |
PLCB4 | Phospholipase C Beta 4 (PLCB4) |
PV | Papillomaviruses |
SF3B1 | Splicing Factor 3B Subunit 1 |
SIRT | Selective Internal Radiotherapy |
SRSF2 | Serine and Arginine Rich Splicing Factor 2 |
TACE | Transarterial Chemoembolization |
TCR | T-cell Receptor |
TEBE | Tebentafusp |
TMB | Tumour Mutational Burden |
UM | Uveal Melanoma |
UVR | Ultraviolet Radiation |
VEGF | Vascular Endothelial Growth Factor |
VLP | Viral-Like Particles |
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Therapy | Mechanism | Efficacy | Limitations | Source(s) |
---|---|---|---|---|
Partial hepatectomy | Surgical resection of metastatic lesions. | Moderate (14–27 months MS) | Only compatible with low liver involvement and well-circumscribed lesions (2–7% of cases). | [44,45] |
Hepatic perfusion and melphalan (isolated/percutaneous) | Local high-dose chemotherapy. | Low (ORR ~20–40%) | Hepatic toxicity; invasive and unrepeatable procedure (isolated). | [46,47] |
Transarterial chemoembolization (TACE) | Local chemotherapy and embolization of the hepatic artery. | Low (~20% ORR, ~15 months MS) | Only compatible with non-diffuse lesions that obtain blood supply solely from the hepatic artery. | [48,49] |
Selective internal radiotherapy (SIRT) | Local radiotherapy (yttrium beads) into the hepatic artery. | Low (~12.3 months OS) | Unsuitable for patients with poor liver function or diffuse lesions. | [50] |
Clinical Trial Reference No. | Treatment | Phase | Status | Note |
---|---|---|---|---|
NCT02697630 | Pembrolizumab (anti-PD-1) + Entinostat (HDAC inhibitor) | II | Completed | Benefits only a subset of patients [78] |
NCT03472586 | Immunoembolization + Ipilimumab (anti-CTLA-4) + nivolumab (anti-PD-1) | II | Completed | Stable disease only (57%) |
NCT04552223 | Nivolumab (anti-PD1) Plus Relatlimab (anti-LAG-3) | II | Active, not recruiting | ORR 7.7% |
NCT05542342 | Sitravatinib (mTKI) and Tislelizumab (anti-PD-1) | II | Active, not recruiting | |
NCT05077280 | Stereotactic Body Radiotherapy + Nivolumab (anti-PD1) + Relatlimab (anti-LAG-3) | II | Active, not recruiting | |
NCT05308901 | Lenvatinib (mTKI) + Pembrolizumab (anti-PD1) | II | Active, not recruiting | |
NCT06519266 | PHP + Ipilimumab (anti-CTLA-4) and Nivolumab (anti-PD-1) | III | Recruiting | |
NCT06121180 | Cemiplimab (anti-PD1) + Ziv-Aflibercept (anti-VEGF) | II | Recruiting | |
NCT06581406 | RP2 (oncolytic immunotherapy) + Nivolumab (anti-PD-1) | II | Recruiting | |
NCT05524935 | Olaparib + Pembrolizumab (anti-PD-1) | II | Recruiting | |
NCT03467516 | Tumour Infiltrating Lymphocytes | II | Recruiting | |
NCT06246149 | Adjuvant Therapeutic: Tebentafusp (IMCgp100) | III | Recruiting |
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Hanratty, K.; Finegan, G.; Rochfort, K.D.; Kennedy, S. Current Treatment of Uveal Melanoma. Cancers 2025, 17, 1403. https://doi.org/10.3390/cancers17091403
Hanratty K, Finegan G, Rochfort KD, Kennedy S. Current Treatment of Uveal Melanoma. Cancers. 2025; 17(9):1403. https://doi.org/10.3390/cancers17091403
Chicago/Turabian StyleHanratty, Katie, Gráinne Finegan, Keith D. Rochfort, and Susan Kennedy. 2025. "Current Treatment of Uveal Melanoma" Cancers 17, no. 9: 1403. https://doi.org/10.3390/cancers17091403
APA StyleHanratty, K., Finegan, G., Rochfort, K. D., & Kennedy, S. (2025). Current Treatment of Uveal Melanoma. Cancers, 17(9), 1403. https://doi.org/10.3390/cancers17091403