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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

Abstract

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.

Keywords

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

Abbreviations

α-MSH

α-Melanocyte-stimulating hormone

AJCC

American Joint Committee on Cancer

BAP1

BRCA1-associated protein

BCUN

1,3-Bis(2-chloroethyl)-1-nitrosourea

CGH

Comparative genomic hybridization

60Co

Cobalt-60

COMS

Collaborative Ocular Melanoma Study

CRNDE

Colorectal neoplasia differentially expressed

CRPs

Complement regulatory proteins

CT

Computed tomography

CTLA-4

Cytotoxic T-lymphocyte-associated protein-4

CYSLTR2

Cysteinyl leukotriene receptor 2

EIF1AX 1A

Eukaryotic translation initiation factor

FDA

Food and Drug Administration

FDG-PET/CT

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

FISH

Fluorescence in situ hybridization

GEP

Gene expression profiling

GM-CSF

Granulocyte–macrophage colony-stimulating factor

GNA11

Guanine nucleotide-binding protein subunit alpha-11

GNAQ

Guanine nucleotide-binding protein G(q) subunit alpha

HDACis

Histone deacetylase inhibitors

HGF

Hepatocyte growth factor

125I

Iodine-125

IFN- γ

Interferon-γ

IGF-1

Insulin-like growth factor-1

IGF-1R

IGF-1 receptor

IHP

Isolated hepatic perfusion

lncRNA

Long non-coding RNA

MAPK

Mitogen-activated protein kinase

MHC

Major histocompatibility complex

MLPA

Multiplex ligation-dependent probe amplification

MRI

Magnetic resonance imaging

MSA

Microsatellite analysis

MUM

Metastatic uveal melanoma

PBT

Proton beam therapy

103Pd

Palladium-103

PD-L1

Programmed death ligand-1

PDT

Photodynamic therapy

PFS

Progression-free survival

PI3K

Phosphatidylinositol 3-kinase

PKC

Protein kinase C

PLCB4

Phospholipase C beta 4

106Ru

Ruthenium-106

SNPs

Single nucleotide polymorphisms

SF3B1

Splicing factor 3b subunit 1

TGF-β

Transforming growth factor β

TTT

Transpupillary thermal therapy

UV

Ultraviolet

VEGF

Vascular endothelial growth factor

VIP

Vasoactive intestinal peptide

YAP

Yes-activated protein

Notes

Acknowledgements

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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