Uveal melanoma: progress in molecular biology and therapeutics.
GNAQ/GNA11 mutation
UM clinical trials
UM signaling pathway
UM-targeted therapy
uveal melanoma
Journal
Therapeutic advances in medical oncology
ISSN: 1758-8340
Titre abrégé: Ther Adv Med Oncol
Pays: England
ID NLM: 101510808
Informations de publication
Date de publication:
2020
2020
Historique:
received:
19
03
2020
accepted:
16
09
2020
entrez:
5
11
2020
pubmed:
6
11
2020
medline:
6
11
2020
Statut:
epublish
Résumé
Uveal melanoma (UM) is the most common intraocular malignancy in adults. So far, no systemic therapy or standard treatment exists to reduce the risk of metastasis and improve overall survival of patients. With the increased knowledge regarding the molecular pathways that underlie the oncogenesis of UM, it is expected that novel therapeutic approaches will be available to conquer this disease. This review provides a summary of the current knowledge of, and progress made in understanding, the pathogenesis, genetic mutations, epigenetics, and immunology of UM. With the advent of the omics era, multi-dimensional big data are publicly available, providing an innovation platform to develop effective targeted and personalized therapeutics for UM patients. Indeed, recently, a great number of therapies have been reported specifically for UM caused by oncogenic mutations, as well as other etiologies. In this review, special attention is directed to advancements in targeted therapies. In particular, we discuss the possibilities of targeting: GNAQ/GNA11, PLCβ, and CYSLTR2 mutants; regulators of G-protein signaling; the secondary messenger adenosine diphosphate (ADP)-ribosylation factor 6 (ARF6); downstream pathways, such as those involving mitogen-activated protein kinase/MEK/extracellular signal-related kinase, protein kinase C (PKC), phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR), Trio/Rho/Rac/Yes-associated protein, and inactivated BAP1; and immune-checkpoint proteins cytotoxic T-lymphocyte antigen 4 and programmed cell-death protein 1/programmed cell-death ligand 1. Furthermore, we conducted a survey of completed and ongoing clinical trials applying targeted and immune therapies for UM. Although drug combination therapy based on the signaling pathways involved in UM has made great progress, targeted therapy is still an unmet medical need.
Identifiants
pubmed: 33149769
doi: 10.1177/1758835920965852
pii: 10.1177_1758835920965852
pmc: PMC7586035
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1758835920965852Informations de copyright
© The Author(s), 2020.
Déclaration de conflit d'intérêts
Conflict of interest statement: The authors declare that there is no conflict of interest.
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