Cancer Chemotherapy and Pharmacology

, Volume 84, Issue 1, pp 15–32 | Cite as

Uveal melanoma: physiopathology and new in situ-specific therapies

  • E. B. SoutoEmail author
  • A. Zielinska
  • M. Luis
  • C. Carbone
  • C. Martins-Gomes
  • S. B. Souto
  • A. M. Silva
Review Article


Uveal melanoma is the most common primary intraocular tumor in adults. It can arise from melanocytes in the anterior (iris) or posterior uveal tract (choroid and ciliary body). Uveal melanoma has a particular molecular pathogenesis, being characterized by specific chromosome alterations and gene mutations (e.g., GNAQ/GNA11; BAP1), which are considered promising targets for molecular therapy. Primary treatment of uveal melanoma includes radiotherapy (brachytherapy and charged-particle therapy), phototherapy (photocoagulation, transpupillary thermal therapy, and photodynamic therapy) and surgery (local resection, enucleation and exenteration). Approximately half of patients with uveal melanoma will, however, develop metastasis, especially in the liver. The treatment of metastatic uveal melanoma includes systemic chemotherapy, immunotherapy and molecular targeted therapy. Liver-directed therapies, such as resection, chemoembolization, immunoembolization, radioembolization, isolated hepatic perfusion and percutaneous hepatic perfusion, are also available to treat metastatic uveal melanoma. Several clinical trials are being developed to study new therapeutic options to treat uveal melanoma, mainly for those with identified liver metastases. The present work discusses the physiopathology and new in situ-specific therapies for the treatment of uveal melanoma.


Uveal melanoma Photocoagulation Transpupillary thermal therapy Photodynamic therapy Liver metastases Liver-directed therapies 



α-Melanocyte-stimulating hormone


American Joint Committee on Cancer


BRCA1-associated protein




Comparative genomic hybridization




Collaborative Ocular Melanoma Study


Colorectal neoplasia differentially expressed


Complement regulatory proteins


Computed tomography


Cytotoxic T-lymphocyte-associated protein-4


Cysteinyl leukotriene receptor 2


Eukaryotic translation initiation factor


Food and Drug Administration


Fluoro-2-deoxy-d-glucose positron emission/CT


Fluorescence in situ hybridization


Gene expression profiling


Granulocyte–macrophage colony-stimulating factor


Guanine nucleotide-binding protein subunit alpha-11


Guanine nucleotide-binding protein G(q) subunit alpha


Histone deacetylase inhibitors


Hepatocyte growth factor



IFN- γ



Insulin-like growth factor-1


IGF-1 receptor


Isolated hepatic perfusion


Long non-coding RNA


Mitogen-activated protein kinase


Major histocompatibility complex


Multiplex ligation-dependent probe amplification


Magnetic resonance imaging


Microsatellite analysis


Metastatic uveal melanoma


Proton beam therapy




Programmed death ligand-1


Photodynamic therapy


Progression-free survival


Phosphatidylinositol 3-kinase


Protein kinase C


Phospholipase C beta 4




Single nucleotide polymorphisms


Splicing factor 3b subunit 1


Transforming growth factor β


Transpupillary thermal therapy




Vascular endothelial growth factor


Vasoactive intestinal peptide


Yes-activated protein



The authors wish to acknowledge the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the projects M-ERA-NET-0004/2015-PAIRED and UID/AGR/04033/2019 (CITAB), co-financed by FEDER, under the Partnership Agreement PT2020. The authors wish to acknowledge the contribution of the Master Student Ms. Irina Pereira in the reading of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors confirm that there is no conflict of interest with respect to the publication of this review.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors. We also confirm that no ethical issues are raised in this work. The research does not involve experiments with humans or with animals.

Informed consent

No inform consent for human participation is needed.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Technology, Faculty of PharmacyUniversity of Coimbra (FFUC)CoimbraPortugal
  2. 2.CEB-Centre of Biological EngineeringUniversity of MinhoBragaPortugal
  3. 3.Laboratory of Drug Delivery Technology, Department of Drug SciencesUniversity of CataniaCataniaItaly
  4. 4.Department of Biology and EnvironmentUniversity of Trás-os-Montes e Alto Douro, UTADVila RealPortugal
  5. 5.Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTADVila RealPortugal
  6. 6.Department of Endocrinology and MetabolismHospital of BragaBragaPortugal

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