Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Treatment of uveal melanoma: where are we now?

ABSTRACT: Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease.

SUBMITTER: Yang J

PROVIDER: S-EPMC5824910 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Treatment of uveal melanoma: where are we now?

Yang Jessica J Manson Daniel K DK Marr Brian P BP Carvajal Richard D RD

Therapeutic advances in medical oncology 20180221

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunothe ...[more]

PMID: 29497459

Similar Datasets

Treatment of Metastatic Uveal Melanoma: Systematic Review.

Project description:INTRODUCTION:More than 50% of patients with uveal melanoma end up developing metastases. Currently, there is no standard first-line treatment that facilitates proper management of the metastatic disease. METHODS:A systematic review of the last 40 years in PubMed with an exhaustive and strict selection of studies was conducted, in which the unit of measurement was overall survival (OS) expressed in Kaplan-Meier curves or numerically. RESULTS:After the selection process, 110 articles were included. Regional therapies, such as intra-arterial liver chemotherapy (OS: 2, 9-22 months), isolated liver perfusion (OS: 9, 6-27, 4 months), or selective internal radiation therapy (OS: 18 months in monotherapy and 26 months in combination with other therapies) showed some superiority when compared to systemic therapies, such as chemotherapy (OS: 4, 6-17 months), immunotherapy (OS: 5-19, 1 month), immunosuppression (OS: 11 months), or targeted therapy (OS: 6-12 months), without being significant. CONCLUSIONS:The results of this review suggest that there are no important differences in OS when comparing the different current treatment modalities. Most of the differences found seem to be explained by the heterogenicity of the different studies and the presence of biases in their design, rather than actual extensions of patient survival.

| S-EPMC7565536 | biostudies-literature

Current and emerging treatment options for uveal melanoma.

Project description:Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults, with a 10-year cumulative metastatic rate of 34%. The most common site of metastasis is the liver (95%). Unfortunately, the current treatment of metastatic UM is limited by the lack of effective systemic therapy. Options for the management of the primary intraocular tumor include radical surgery as well as conservative treatments in order to preserve visual acuity. For metastatic disease, several approaches have been described with no standard method. Nevertheless, median survival after liver metastasis is poor, being around 4-6 months, with a 1-year survival of 10%-15%. In this review, the authors summarize current and promising new treatments for UM.

| S-EPMC3755706 | biostudies-literature

Darovasertib, a novel treatment for metastatic uveal melanoma.

Project description:The FDA granted orphan drug designation to darovasertib, a first-in-class oral, small molecular inhibitor of protein kinase C (PKC), for the treatment of uveal melanoma, on 2 May 2022. Primary uveal melanoma has a high risk of progressing to metastatic uveal melanoma, with a poor prognosis. The activation of the PKC and mitogen-activated protein kinase pathways play an essential role in the pathogenesis of uveal melanoma, and mutations in the G protein subunit alpha q (GNAQ), and G protein subunit alpha11 (GNA11) genes are considered early events in the development of uveal melanoma. Compared to other PKC inhibitors, such as sotrastaurin and enzastaurin, darovasertib is significantly more potent in inhibiting conventional (α, β) and novel (δ, ϵ, η, θ) PKC proteins and has a better tolerability and safety profile. Current Phase I/II clinical trials indicated that darovasertib, combined with the Mitogen-activated protein kinase/Extracellular (MEK) inhibitors, binimetinib or crizotinib, produced a synergistic effect of uveal melanoma. In this article, we summarize the development of drugs for treating uveal melanomas and discuss problems associated with current treatments. We also discuss the mechanism of action, pharmacokinetic profile, adverse effects, and clinical trial for darovasertib, and future research directions for treating uveal melanoma.

| S-EPMC10419210 | biostudies-literature

Metastatic Uveal Melanoma: Treatment Strategies and Survival-Results from the Dutch Melanoma Treatment Registry.

Project description:Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Up to 50% of UM patients will develop metastases. We present data of 175 metastatic UM patients diagnosed in the Netherlands between July 2012 and March 2018. In our cohort, elevated lactate dehydrogenase level (LDH) is an important factor associated with poorer survival (Hazard Ratio (HR) 9.0, 95% Confidence Interval (CI) 5.63-14.35), and the presence of liver metastases is negatively associated with survival (HR 2.09, 95%CI 1.07-4.08). We used data from the nation-wide Dutch Melanoma Treatment Registry (DMTR) providing a complete overview of the location of metastases at time of stage IV disease. In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases. In 63 (36%) patients, mutation analysis was performed, showing a GNA11 mutation in 28.6% and a GNAQ mutation in 49.2% of the analyzed patients. In the absence of standard care of treatment options, metastatic UM patients are often directed to clinical trials. Patients participating in clinical trials are often subject to selection and usually do not represent the entire metastatic UM population. By using our nation-wide cohort, we are able to describe real-life treatment choices made in metastatic UM patients and 1-year survival rates in selected groups of patients.

| S-EPMC6678641 | biostudies-literature

Uveal melanoma: epidemiology, etiology, and treatment of primary disease.

Project description:Uveal melanoma (UM) is the most common intraocular malignancy and arises from melanocytes in the iris, ciliary body, or choroid. Early diagnosis and local treatment is crucial, as survival correlates with primary tumor size. However, approximately 50% of patients will develop metastatic disease with 6-12 months' survival from metastatic diagnosis. Genomic analyses have led to the development of gene-expression profiles that effectively predict metastatic progression; unfortunately, no adjuvant therapy has been shown to prolong survival to date. New insights into the molecular biology of UM have found frequent activating mutations in genes encoding for the G-protein ?-subunit, GNAQ and GNA11, and improved understanding of the downstream signaling pathways MAPK, PI3K/Akt, and Hippo have afforded an array of new targets for treatment of this disease. Studies are under way with rationally developed regimens targeting these pathways, and novel agents are under development. We review the diagnosis, management, and surveillance of primary UM and the adjuvant therapy trials under way.

| S-EPMC5298817 | biostudies-literature

Uveal Melanoma Metastasis.

Project description:Uveal melanoma (UM) is characterized by relatively few, highly incident molecular alterations and their association with metastatic risk is deeply understood. Nevertheless, this knowledge has so far not led to innovative therapies for the successful treatment of UM metastases or for adjuvant therapy, leaving survival after diagnosis of metastatic UM almost unaltered in decades. The driver mutations of UM, mainly in the G-protein genes GNAQ and GNA11, activate the MAP-kinase pathway as well as the YAP/TAZ pathway. At present, there are no drugs that target the latter and this likely explains the failure of mitogen activated kinase kinase inhibitors. Immune checkpoint blockers, despite the game changing effect in cutaneous melanoma (CM), show only limited effects in UM probably because of the low mutational burden of 0.5 per megabase and the unavailability of antibodies targeting the main immune checkpoint active in UM. The highly pro-tumorigenic microenvironment of UM also contributes to therapy resistance. However, T-cell redirection by a soluble T-cell receptor that is fused to an anti-CD3 single-chain variable fragment, local, liver specific therapy, new immune checkpoint blockers, and YAP/TAZ specific drugs give new hope to repeating the success of innovative therapy obtained for CM.

| S-EPMC8616038 | biostudies-literature

Metastatic disease from uveal melanoma: treatment options and future prospects.

Project description:Uveal melanoma represents ?85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care.

| S-EPMC5256122 | biostudies-literature

Immunotherapies for the Treatment of Uveal Melanoma-History and Future.

Project description:Uveal melanoma is the most common primary intraocular malignancy among adults. It is, nevertheless, a rare disease, with an incidence of approximately one case per 100,000 individuals per year in Europe. Approximately half of tumors will eventually metastasize, and the liver is the organ usually affected. No standard-of-care treatment exists for metastasized uveal melanoma. Chemotherapies or liver-directed treatments do not usually result in long-term tumor control. Immunotherapies are currently the most promising therapy option available. We reviewed both relevant recent literature on PubMed concerning the treatment of uveal melanoma with immunotherapies, and currently investigated drugs on ClinicalTrials.gov. Our own experiences with immune checkpoint blockers are included in a case series of 20 patients. Because few clinical trials have been conducted for metastasized uveal melanoma, no definitive treatment strategy exists for this rare disease. The outcomes of most immunotherapies are poor, especially compared with cutaneous melanoma. However, encouraging results have been found for some very recently investigated agents such as the bispecific tebentafusp, for which a remarkably increased one-year overall survival rate, and similarly increased disease control rate, were observed in early phase studies. The treatment of metastatic uveal melanoma remains challenging, and almost all patients still die from the disease. Long-term responses might be achievable by means of new immunological strategies. Patients should therefore be referred to large medical centers where they can take part in controlled clinical studies.

| S-EPMC6721437 | biostudies-literature

Pembrolizumab for the treatment of uveal melanoma: A case series.

Project description:Uveal melanoma is a rare disease. Up to 50% of the patients will develop metastases for which the treatment options are limited. No randomized controlled data for the treatment of uveal melanoma patients are available. In this study we describe the clinical course of nine uveal melanoma patients included in the pembrolizumab expanded access program (EAP) in Belgium. Nine uveal melanoma patients were treated in the EAP with 2mg/kg pembrolizumab every 3 weeks. Patients received pembrolizumab as first or second-line treatment. Baseline characteristics and tumor responses were prospectively collected. During a median follow-up of 40 weeks, the estimated median PFS was 18 weeks (95% CI 0.7-35) and median OS was 46 weeks (95% CI 33-59%). Four patients had stable disease (SD) for more than 20 weeks (PFS of 21, 22, and 27 weeks respectively) and 1 patient presented with SD for 119 weeks. No objective responses according to irRC were observed. One grade 3 hepatitis occurred which was reversible with the administration of high doses oral corticosteroids. Even though treatment with pembrolizumab is well tolerated, clinical benefit is disappointing. Nevertheless long-term diseases control can be achieved in selected cases.

| S-EPMC7675863 | biostudies-literature

Tebentafusp: a first-in-class treatment for metastatic uveal melanoma.

Project description:Tebentafusp is a first-in-class immunotherapy agent that comprises an engineered T-cell receptor targeting a gp100 epitope presented by human leukocyte antigen-A*02:01 cells, fused to an anti-CD3 single-chain variable fragment. Tebentafusp is both the first bispecific T-cell engager to show efficacy in the treatment of advanced solid cancer and the first anti-cancer treatment to demonstrate an overall survival benefit in patients with uveal melanoma (UM). This review article will focus on the clinical development of tebentafusp, the mechanism of action and resultant evolution of the management of advanced UM.

| S-EPMC10031621 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data