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

Anastasia Gkiala,1 Sotiria Palioura2 1National and Kapodistrian University of Athens School of Medicine, Athens, Greece; 2Athens Vision Eye Institute, Athens, GreeceCorrespondence: Sotiria PaliouraAthens Vision Eye Institute, 328-330 Syngrou Ave., Kallithea, Athens 17673, GreeceTel +30 698 580 2355E...

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Autores principales:	Gkiala A, Palioura S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	immune checkpoint inhibitors braf inhibitors mek inhibitors ctla4 inhibitors pd1 inhibitors c-kit mutations braf mutations nras mutations dabrafenib vemurafenib trametinib ipilimumab pembrolizumab nivolumab Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/96d740eef50a4661b616ed467f3e7953
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spelling	oai:doaj.org-article:96d740eef50a4661b616ed467f3e79532021-12-02T13:16:22ZConjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies1177-5483https://doaj.org/article/96d740eef50a4661b616ed467f3e79532020-10-01T00:00:00Zhttps://www.dovepress.com/conjunctival-melanoma-update-on-genetics-epigenetics-and-targeted-mole-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Anastasia Gkiala,1 Sotiria Palioura2 1National and Kapodistrian University of Athens School of Medicine, Athens, Greece; 2Athens Vision Eye Institute, Athens, GreeceCorrespondence: Sotiria PaliouraAthens Vision Eye Institute, 328-330 Syngrou Ave., Kallithea, Athens 17673, GreeceTel +30 698 580 2355Email sotiria.palioura@gmail.comPurpose: 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, nivolumabGkiala APalioura SDove Medical Pressarticleimmune checkpoint inhibitorsbraf inhibitorsmek inhibitorsctla4 inhibitorspd1 inhibitorsc-kit mutationsbraf mutationsnras mutationsdabrafenibvemurafenibtrametinibipilimumabpembrolizumabnivolumabOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 14, Pp 3137-3152 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune checkpoint inhibitors braf inhibitors mek inhibitors ctla4 inhibitors pd1 inhibitors c-kit mutations braf mutations nras mutations dabrafenib vemurafenib trametinib ipilimumab pembrolizumab nivolumab Ophthalmology RE1-994
spellingShingle	immune checkpoint inhibitors braf inhibitors mek inhibitors ctla4 inhibitors pd1 inhibitors c-kit mutations braf mutations nras mutations dabrafenib vemurafenib trametinib ipilimumab pembrolizumab nivolumab Ophthalmology RE1-994 Gkiala A Palioura S Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies
description	Anastasia Gkiala,1 Sotiria Palioura2 1National and Kapodistrian University of Athens School of Medicine, Athens, Greece; 2Athens Vision Eye Institute, Athens, GreeceCorrespondence: Sotiria PaliouraAthens Vision Eye Institute, 328-330 Syngrou Ave., Kallithea, Athens 17673, GreeceTel +30 698 580 2355Email sotiria.palioura@gmail.comPurpose: 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
format	article
author	Gkiala A Palioura S
author_facet	Gkiala A Palioura S
author_sort	Gkiala A
title	Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies
title_short	Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies
title_full	Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies
title_fullStr	Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies
title_full_unstemmed	Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies
title_sort	conjunctival melanoma: update on genetics, epigenetics and targeted molecular and immune-based therapies
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/96d740eef50a4661b616ed467f3e7953
work_keys_str_mv	AT gkialaa conjunctivalmelanomaupdateongeneticsepigeneticsandtargetedmolecularandimmunebasedtherapies AT paliouras conjunctivalmelanomaupdateongeneticsepigeneticsandtargetedmolecularandimmunebasedtherapies
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Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies

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