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Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies

Authors Gkiala A, Palioura S

Received 9 July 2020

Accepted for publication 17 September 2020

Published 9 October 2020 Volume 2020:14 Pages 3137—3152


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Scott Fraser

Anastasia Gkiala,1 Sotiria Palioura2

1National and Kapodistrian University of Athens School of Medicine, Athens, Greece; 2Athens Vision Eye Institute, Athens, Greece

Correspondence: Sotiria Palioura
Athens Vision Eye Institute, 328-330 Syngrou Ave., Kallithea, Athens 17673, Greece
Tel +30 698 580 2355

Purpose: To present the molecular mechanisms involved in the pathogenesis of conjunctival melanoma (CM) and review the existing literature on targeted molecular inhibitors as well as immune checkpoint inhibitors for the management of locally advanced and metastatic disease.
Methods: A comprehensive review of the literature was performed using the keywords “conjunctival melanoma”, “immune checkpoint inhibitors”, “BRAF inhibitors”, “MEK inhibitors”, “CTLA4 inhibitors”, “PD1 inhibitors”, “c-KIT mutations”, “BRAF mutations”, “NRAS mutations”, “dabrafenib”, “trametinib”, “vemurafenib”, “ipilimumab”, “pembrolizumab”, and “nivolumab”. A total of 250 articles were reviewed and 120 were included in this report.
Results: Mutations of mediators in the MAP kinase pathway, such as RAS, BRAF, MEK and ERK, and mutations of the PI3K/AKT/mTOR pathway play a major role in the pathogenesis of conjunctival melanoma. In addition, alterations of c-KIT, NF1, TERT, chemokine receptors as well as chromosomal copy number alterations and micro RNAs are thought to have a causative association with CM development. Targeted molecular inhibitors, such as BRAF and MEK inhibitors, are currently being implemented in the therapy of BRAF-mutated CM. Furthermore, immune checkpoint PD-1 and CTLA4 inhibitors with favorable clinical outcomes in the treatment of cutaneous melanoma have increased recurrence-free survival and reduced metastatic spread in CM cases.
Conclusion: The complex molecular mechanisms that contribute to the development of CM can be targeted both by molecular inhibitors of oncogenic pathways as well as immune checkpoint inhibitors in order to halt progression of the disease and increase survival.

Keywords: immune checkpoint inhibitors, BRAF inhibitors, MEK inhibitors, CTLA4 inhibitors, PD1 inhibitors, c-KIT mutations, BRAF mutations, NRAS mutations, dabrafenib, vemurafenib, trametinib, ipilimumab, pembrolizumab, nivolumab

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