Genetics of Uveal Melanoma and Cutaneous Melanoma: Two of a Kind?

Bosch, Thomas van den; Kılıç, Emine; Paridaens, Dion; Klein, Annelies de

doi:10.1155/2010/360136

Cited by 62 publications

(44 citation statements)

References 122 publications

(151 reference statements)

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“…Mutation of BRCA1-associated protein 1 (BAP1), located on chromosome 3p21, was frequently identified in metastatic UM [19][20][21] . Particularly, it was reported that BAP1 mutation in UM cells may cause the liver tropism [22] .…”

Section: Chromosomal and Genetic Abnormalitiesmentioning

confidence: 99%

Immunological aspect of the liver and metastatic uveal melanoma

Terai¹,

Mastrangleo²,

Sato³

2017

JCMT

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Uveal (eye) melanoma is the most common primary eye malignancy in adults. Despite optimal treatments for primary uveal melanoma, up to 50% of patients subsequently develop systemic metastasis, often in the liver. Once hepatic metastasis develops, the survival of patients is generally short and currently available treatments fail to show meaningful improvement of survival. Recent development of immune checkpoint blockades revolutionized immunotherapy for metastatic cutaneous (skin) melanoma. Unfortunately, metastatic uveal melanoma is unresponsive to this approach, thus there is an unmet need to improve the treatment of metastatic uveal melanoma. One unique characteristic of uveal melanoma is that the majority of metastases first develop in the liver. The liver is highly specialized in development of immune tolerance to food-derived antigens and consequently serves a unique function in the immune system. Understanding the mechanisms by which the liver orchestrates immune-related responses is important to the development of an effective immunotherapy for hepatic metastases such as metastatic uveal melanoma. In this review article, the authors overview the immunological aspects of the liver and discuss approaches to improve immunotherapy for metastatic uveal melanoma. Key words:Uveal melanoma, metastasis, liver, liver microenvironment, immunotherapy ABSTRACTArticle history:

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Section: Chromosomal and Genetic Abnormalitiesmentioning

confidence: 99%

Immunological aspect of the liver and metastatic uveal melanoma

Terai¹,

Mastrangleo²,

Sato³

2017

JCMT

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“…23 However, these 2 tumors show remarkable differences in their metastatic spread and therapeutic response. 38,39 The same applies to their associated genetic findings: more than 80% of uveal melanomas carry mutations in GNA11 or GNAQ; in cutaneous melanoma, oncogenic mutations in BRAF and NRAS seem to be primarily involved. 15,40,41 However, both GNAQ/GNA11 and BRAF/NRAS activate a common pathway, the mitogen-activated protein kinase (MAPK).…”

Section: Study Populationmentioning

confidence: 99%

Second Primary Neoplasms in Patients With Uveal Melanoma: A SEER Database Analysis

Bartosch

Mondim

Healy

et al. 2016

American Journal of Ophthalmology

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PURPOSE: To determine the risk of second primary neoplasms (SPNs) in subjects previously diagnosed with uveal melanoma (UM), including an analysis on whether radiotherapy is a risk factor to develop these SPNs.DESIGN: Retrospective cohort study. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) 9 database, we identified patients diagnosed with UM as their first malignancy between 1973 and 2011 (n [ 3976). We obtained standardized incidence ratios (SIR) and excess absolute risks of SPNs on patients with UM compared to a reference population. Multivariate Cox regression models were used to evaluate the effect of radiotherapy in SPN risk.RESULTS: Sixteen percent (n [ 641) of the patients developed SPNs during a median follow-up of 83 months (range, 1-463 months). This represented an 11% excess risk compared to the reference population, mainly owing to a significantly increased risk of skin melanomas (SIR [ 2.93, 95% CI: 2.23-3.78) and kidney tumors (SIR [ 1.91, 95% CI: 1.27-2.76), primarily in those diagnosed between 30 and 59 years of age. The occurrence of second UM was also increased (SIR [ 16.90, 95% CI: 9.00-28.90), which likely includes recurrences misclassified as a second cancer. Radiotherapy was performed in 39% (n [ 1538) of the patients. Multivariate analysis revealed that this treatment was not an independent risk factor for SPNs (hazard ratio [ 1.06, 95% CI: 0.88-1.26, P [ .54).CONCLUSIONS: Patients with UM presented an 11% higher risk of SPNs compared to the reference population. Radiotherapy does not seem to be a risk factor. SPNs should be considered in the surveillance of UM. (Am J Ophthalmol 2016;165:54-64. Ó 2016 Elsevier Inc. All rights reserved.) P UBLISHED DATA ON SURVIVAL OF UVEAL MELAnoma demonstrate that more than half of the patients are long-term survivors. At 5 and 10 years, the survival rates range between 68%-82% and 57%-62%, respectively.

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“…Nowadays the clinical treatment of uveal melanoma is mainly surgery and radiotherapy, systemic chemotherapy is only used in some advanced cases with metastasis. 1 Here we choose the combination of chemotherapy rather than radiotherapy and adenovirus is intended to explore a new way of topical chemotherapy plus topical injection of oncolytic virus to treat uveal melanoma. Next, some studies of the described combination treatment for other tumor type observed an augmentation of apoptosis [12][13][14][15] while our investigation demonstrated that whether monotherapy of DTIC or H101, or co-treatment appears to be related to cell cycle blocking instead of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…1 Survival rates for UM remain poor due to the high frequency of metastases exhibiting significant resistance to systemic therapy, with median survival less than 6 months. 2 It is well-established that the primary goal of treating UM is to prevent metastases and save lives, followed secondarily by reserving the eyeball and vision.…”

Section: Introductionmentioning

confidence: 99%

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Cun¹,

Song²,

Jia³

et al. 2012

Cancer Biology & Therapy

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These authors contributed equally to this work.Keywords: uveal melanoma, oncolytic adenovirus, dacarbazine, combination therapy, cell cycle Uveal melanoma is the most common primary intraocular malignancy in adults; however, current therapeutic modalities, including chemotherapy, have not been successful. Oncolytic viruses serve as an emerging gene therapy tool for cancer treatment because they specifically kill tumor cells while sparing normal cells. The oncolytic virus H101 has been approved by the Chinese State Food and Drug Administration for the treatment of certain malignancies. Unfortunately, the monotherapy of adenovirus has demonstrated limited efficacy in a clinical setting. Thus, novel treatment strategies in which an oncolytic virus is combined with existing chemicals are advancing toward potential clinical use. In this study, we chose the combination of oncolytic virus H101 and the alkylating agent dacarbazine (DTIC) to treat uveal melanoma cells in vitro. Our results demonstrated that the combination exerted a synergistic antitumor effect without enhanced toxicity to normal cells via a type of cell cycle block other than the induction of apoptosis. Further investigation is warranted to elucidate the specific underlying mechanisms of this co-treatment therapy. Our study suggests the virochemo combination therapy is feasible and is a potentially promising approach for the treatment of uveal melanoma.

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Genetics of Uveal Melanoma and Cutaneous Melanoma: Two of a Kind?

Cited by 62 publications

References 122 publications

Immunological aspect of the liver and metastatic uveal melanoma

Immunological aspect of the liver and metastatic uveal melanoma

Second Primary Neoplasms in Patients With Uveal Melanoma: A SEER Database Analysis

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

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