Vol.:(0123456789) 1 3 Cancer Chemotherapy and Pharmacology (2019) 84:15–32 https://doi.org/10.1007/s00280-019-03860-z REVIEW ARTICLE Uveal melanoma: physiopathology and new in situ‑specifc therapies E. B. Souto 1,2  · A. Zielinska 1  · M. Luis 1  · C. Carbone 1,3  · C. Martins‑Gomes 4,5  · S. B. Souto 6  · A. M. Silva 4,5 Received: 20 December 2018 / Accepted: 2 May 2019 / Published online: 11 May 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 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 specifc 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, immu- noembolization, 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 identifed liver metastases. The present work discusses the physiopathology and new in situ-specifc 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 60 Co Cobalt-60 COMS Collaborative Ocular Melanoma Study CRNDE Colorectal neoplasia diferentially 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 profling GM-CSF Granulocyte–macrophage colony-stimu- lating factor GNA11 Guanine nucleotide-binding protein subu- nit alpha-11 GNAQ Guanine nucleotide-binding protein G(q) subunit alpha HDACis Histone deacetylase inhibitors * E. B. Souto ebsouto@ebsouto.pt 1 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal 2 CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal 3 Laboratory of Drug Delivery Technology, Department of Drug Sciences, University of Catania, Catania, Italy 4 Department of Biology and Environment, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal 5 Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal 6 Department of Endocrinology and Metabolism, Hospital of Braga, Sete Fontes, São Victor, 4710-243 Braga, Portugal