Uveal melanoma: physiopathology and new in situ-specific therapies

Cancer Chemother Pharmacol. 2019 Jul;84(1):15-32. doi: 10.1007/s00280-019-03860-z. Epub 2019 May 11.

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

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Chromosome Aberrations
  • GTP-Binding Protein alpha Subunits / genetics
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics
  • Humans
  • Liver Neoplasms / secondary
  • Liver Neoplasms / therapy*
  • Melanoma / genetics
  • Melanoma / pathology*
  • Melanoma / therapy
  • Mutation
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / genetics
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / pathology*
  • Uveal Neoplasms / therapy

Substances

  • BAP1 protein, human
  • GNA11 protein, human
  • GNAQ protein, human
  • GTP-Binding Protein alpha Subunits
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase
  • GTP-Binding Protein alpha Subunits, Gq-G11

Supplementary concepts

  • Uveal melanoma