TY - JOUR

T1 - Conjunctival melanoma

T2 - New insights in tumour genetics and immunology, leading to new therapeutic options

AU - Brouwer, Niels J.

AU - Verdijk, Robert M.

AU - Heegaard, Steffen

AU - Marinkovic, Marina

AU - Esmaeli, Bita

AU - Jager, Martine J.

N1 - Funding Information: This work was supported by the following foundations: Leiden University Medical Center (MD/PhD program grant, NJB), and European Commission (Horizon, 2020 grant number 667787 , NJB, MJJ). Publisher Copyright: © 2021

PY - 2022/1

Y1 - 2022/1

N2 - Recent developments in oncology have led to a better molecular and cellular understanding of cancer, and the introduction of novel therapies. Conjunctival melanoma (CoM) is a rare but potentially devastating disease. A better understanding of CoM, leading to the development of novel therapies, is urgently needed. CoM is characterized by mutations that have also been identified in cutaneous melanoma, e.g. in BRAF, NRAS and TERT. These mutations are distinct from the mutations found in uveal melanoma (UM), affecting genes such as GNAQ, GNA11, and BAP1. Targeted therapies that are successful in cutaneous melanoma may therefore be useful in CoM. A recent breakthrough in the treatment of patients with metastatic cutaneous melanoma was the development of immunotherapy. While immunotherapy is currently sparsely effective in intraocular tumours such as UM, the similarities between CoM and cutaneous melanoma (including in their immunological tumour micro environment) provide hope for the application of immunotherapy in CoM, and preliminary clinical data are indeed emerging to support this use. This review aims to provide a comprehensive overview of the current knowledge regarding CoM, with a focus on the genetic and immunologic understanding. We elaborate on the distinct position of CoM in contrast to other types of melanoma, and explain how new insights in the pathophysiology of this disease guide the development of new, personalized, treatments.

AB - Recent developments in oncology have led to a better molecular and cellular understanding of cancer, and the introduction of novel therapies. Conjunctival melanoma (CoM) is a rare but potentially devastating disease. A better understanding of CoM, leading to the development of novel therapies, is urgently needed. CoM is characterized by mutations that have also been identified in cutaneous melanoma, e.g. in BRAF, NRAS and TERT. These mutations are distinct from the mutations found in uveal melanoma (UM), affecting genes such as GNAQ, GNA11, and BAP1. Targeted therapies that are successful in cutaneous melanoma may therefore be useful in CoM. A recent breakthrough in the treatment of patients with metastatic cutaneous melanoma was the development of immunotherapy. While immunotherapy is currently sparsely effective in intraocular tumours such as UM, the similarities between CoM and cutaneous melanoma (including in their immunological tumour micro environment) provide hope for the application of immunotherapy in CoM, and preliminary clinical data are indeed emerging to support this use. This review aims to provide a comprehensive overview of the current knowledge regarding CoM, with a focus on the genetic and immunologic understanding. We elaborate on the distinct position of CoM in contrast to other types of melanoma, and explain how new insights in the pathophysiology of this disease guide the development of new, personalized, treatments.

KW - Conjunctival melanoma

KW - Eye disease

KW - Immunotherapy

KW - Ocular oncology

KW - Oncogenetics

KW - Targeted therapy

U2 - 10.1016/j.preteyeres.2021.100971

DO - 10.1016/j.preteyeres.2021.100971

M3 - Review

C2 - 34015548

AN - SCOPUS:85106625089

VL - 86

JO - Progress in Retinal and Eye Research

JF - Progress in Retinal and Eye Research

SN - 1350-9462

M1 - 100971

ER -