Treatment strategies for clinically detectable metastatic uveal melanoma

2014 ◽  
pp. 168-190
Author(s):  
Aakanksha Prasad Asija ◽  
Makoto Yoshida ◽  
Takami Sato
Keyword(s):  
Uveal Melanoma ◽  
Treatment Strategies

scholarly journals The Tumorigenic Properties of EZH2 are Mediated by MiR-26a in Uveal Melanoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Yao Li ◽  
Mingmei Zhang ◽  
Huayin Feng ◽  
Shaya Mahati
Keyword(s):  
Uveal Melanoma ◽  
Cell Function ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Polycomb Group ◽  
Luciferase Reporter ◽  
Polycomb Group Protein ◽  
Ezh2 Expression ◽  
Group Protein ◽  
Tumor Types

Background: The polycomb group protein enhancer of zeste homolog 2 (EZH2) has been found to be highly expressed in various tumors, and microRNA-26a (miR-26a) is often unmodulated in cancers. However, the functions of these two molecules in uveal melanoma (UM) and their relationships have not been reported.Methods: We explored the effects of the miR-26a–EZH2 axis in UM by examining the levels of miR-26a and EZH2. The EZH2 levels in various tumor types and the correlations between EZH2 levels and overall survival and disease-free survival were reanalyzed. The binding of miR-26a to the 3′-untranslated region of EZH2 mRNA was measured using the luciferase reporter assay. The regulation of EZH2 gene expression by miR-26a was also identified, and the effect of elevated EZH2 expression on UM cell function was further examined. Results: miR-26a was downregulated and EZH2 was upregulated in UM cells. Overexpression of miR-26a inhibited cell proliferation, and knockdown of EZH2 suppressed cell growth. EZH2 was a direct target of miR-26a in UM cells. The knockout of EZH2 mimicked the tumor inhibition of miR-26a in UM cells, whereas the reintroduction of EZH2 abolished this effect. In addition, a network of EZH2 and its interacting proteins (UBC, CDK1, HDAC1, SUZ12, EED) was found to participate in miR-26a-mediated tumor progression.Conclusion: The newly identified miR-26a–EZH2 axis may be a potential target for the development of treatment strategies for UM.

scholarly journals Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Vidhya Karivedu ◽  
Ihab Eldessouki ◽  
Ahmad Taftaf ◽  
Zheng Zhu ◽  
Abouelmagd Makramalla ◽  
...  
Keyword(s):  
Partial Response ◽  
Clinical Outcome ◽  
Uveal Melanoma ◽  
Stable Disease ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Treatment Strategies ◽  
Case Series ◽  
Retrospective Case ◽  
Study Results

Background. Metastatic uveal melanoma (MUM) is associated with a poor prognosis, with a median overall survival (OS) of 4–15 months. Despite new insights into the genetic and molecular background of MUM, satisfactory systemic treatment approaches are currently lacking. The study results of innovative treatment strategies are urgently needed. Patients and Methods. This was a retrospective case series of 8 patients with MUM managed at the University of Cincinnati between January 2015 and January 2018. The immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria were used for patient evaluation, and magnetic resonance imaging was used for evaluation at treatment checkpoints. Objective. To assess the clinical outcome of patients with MUM treated with a combination of checkpoint inhibitors. Results. The series included eight patients, six men and two women, with MUM. Their median age at MUM diagnosis was 69 (range, 55–77) years. All patients were treated with ipilimumab and nivolumab combination along with transarterial chemoembolization (TACE), followed by nivolumab maintenance and monthly TACE procedures. The majority of patients had a partial response or stable disease. Two of the patients had partial response, while four others had stable disease. Two other patients experienced disease progression. Conclusion. We report the outcomes of eight patients with MUM treated with the combination of ipilimumab and nivolumab. We report the clinical outcome and toxicity associated with this treatment approach. Further studies are warranted to explore immunotherapy in MUM. These findings support the consideration of immunotherapy in MUM.

scholarly journals Epidemiology of uveal melanoma in Brazil

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Evandro Lucena ◽  
Daniel Cohen Goldemberg ◽  
Luiz Claudio Santos Thuler ◽  
Andreia Cristina de Melo
Keyword(s):  
Sex Education ◽  
Uveal Melanoma ◽  
Healthcare Access ◽  
Regional Distribution ◽  
Age Distribution ◽  
Treatment Strategies ◽  
Distant Metastases ◽  
Cancer Registries ◽  
Clinical Staging ◽  
Continuous Variables

Abstract Purpose To report the prevalence of uveal melanoma in a Hospital database in Brazil over the period of 16 years (2000 to 2016). Design Descriptive epidemiological study evaluating the Brazilian Hospital Based Cancer Registries. Participants/methods Uveal melanomas were identified based on ICD-O-3 codes C69.3 [choroid], C69.4 [ciliary body and iris], and C69.2 [retina]) derived from the Integrator Registry database. Kolmogorov–Smirnov Test was used for evaluation of normality of data, t-test and Chi square were used for categorical and continuous variables respectively using SPSS Software. Main outcome measures Age, sex, education, regional distribution, clinical staging at the diagnosis, time from diagnosis to treatment (≤ 60 days versus > 60 days) and first-course therapy (surgery, chemotherapy, radiotherapy or a combination of such). Results There were 2166 cases of uveal melanoma representing 5.4% of all cases of melanoma. Histological confirmation of uveal melanoma was available in all cases. Higher prevalence of 1139 cases (52.6%) in women than 1027 cases (47.4%) in men was observed. Age distribution revealed 1411 cases (65.1%) in the group between 41 and 69 years old. A total of 429 (19.8%) patients were classified as initial disease and 334 (15.4%) as advanced (regional or distant metastases). Staging as initial disease was more frequent (113–24.8%) in patients with > 8 school years than in patients with < 8 school years (179–17.6%) reflecting disparities in healthcare access between those two populations. No difference was noticed in terms of diagnosis, staging and treatment after the Brazilian “60 days law” (Federal Law 12.732/12) came into effect in 2013 regulating the maximum period that a patient with cancer has to wait until start the treatment. Conclusion Epidemiological data is critical for planning early treatment strategies and allocating medical resources. This study intended to understand the characteristics of uveal melanoma in Brazil.

scholarly journals New Perspectives for Eye-Sparing Treatment Strategies in Primary Uveal Melanoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 134
Author(s):  
Krzysztof Bilmin ◽  
Kamil J. Synoradzki ◽  
Anna M. Czarnecka ◽  
Mateusz J. Spałek ◽  
Tamara Kujawska ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Uveal Melanoma ◽  
Focused Ultrasound ◽  
Early Stage ◽  
Treatment Options ◽  
Treatment Strategies ◽  
High Intensity Focused Ultrasound ◽  
Local Concentration ◽  
Proton Beam Radiotherapy ◽  
Stage Of Development

Uveal melanoma is the most common intraocular malignancy and arises from melanocytes in the choroid, ciliary body, or iris. The current eye-sparing treatment options include surgical treatment, plaque brachytherapy, proton beam radiotherapy, stereotactic photon radiotherapy, or photodynamic therapy. However, the efficacy of these methods is still unsatisfactory. This article reviews several possible new treatment options and their potential advantages in treating localized uveal melanoma. These methods may be based on the physical destruction of the cancerous cells by applying ultrasounds. Two examples of such an approach are High-Intensity Focused Ultrasound (HIFU)—a promising technology of thermal destruction of solid tumors located deep under the skin and sonodynamic therapy (SDT) that induces reactive oxygen species. Another approach may be based on improving the penetration of anti-cancer agents into UM cells. The most promising technologies from this group are based on enhancing drug delivery by applying electric current. One such approach is called transcorneal iontophoresis and has already been shown to increase the local concentration of several different therapeutics. Another technique, electrically enhanced chemotherapy, may promote drug delivery from the intercellular space to cells. Finally, new advanced nanoparticles are developed to combine diagnostic imaging and therapy (i.e., theranostics). However, these methods are mostly at an early stage of development. More advanced and targeted preclinical studies and clinical trials would be needed to introduce some of these techniques to routine clinical practice.

scholarly journals Epigenetic Changes in Malignant Uveal Melanoma and Possibilities of Their Therapeutic Targeting

2020 ◽  
Vol 76 (2) ◽  
pp. 103-110
Author(s):  
Božena Smolková ◽  
Lucia Demková
Keyword(s):  
Uveal Melanoma ◽  
Histone Deacetylase Inhibitors ◽  
Treatment Strategies ◽  
Epigenetic Changes ◽  
Cycle Arrest ◽  
Risk Patients ◽  
New Treatment ◽  
Malignant Uveal Melanoma ◽  
Traditional Approaches ◽  
Effective Drugs

Uveal melanoma (UM) is a deadly cancer that leads to metastatic disease in more than 50 % of the patients. Despite the improvement in the treatment of primary disease, there is still no effective therapy to prevent the development of metastases. Therefore, the disease requires intensive research to identify new treatment strategies. In preclinical UM models, epigenetic drugs have been shown to increase the sensitivity of resistant tumour cells to treatment. The successful use of histone deacetylase inhibitors, which induced cell cycle arrest, reprogramming consistent with melanocyte differentiation and inhibition of tumour growth in preclinical models, demonstrates the role of epigenetic regulation in UM metastasis. Identification of epigenetic changes associated with UM development an progression could contribute to the discovery of more effective drugs that, in combination with traditional approaches, may yield better therapeutic results for high-risk patients.

scholarly journals New Perspectives for Eye-Sparing Treatment Strategies in Primary Uveal Melanoma

2021 ◽  
Author(s):  
Krzysztof Bilmin ◽  
Kamil J. Synoradzki ◽  
Anna M. Czarnecka ◽  
Mateusz J. Spałek ◽  
Tamara Kujawska ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Uveal Melanoma ◽  
Focused Ultrasound ◽  
Genetic Material ◽  
Treatment Strategies ◽  
Antifungal Drugs ◽  
High Intensity Focused Ultrasound ◽  
Local Concentration ◽  
Particle Radiotherapy

Uveal melanoma is the most common intraocular malignancy and arises from melanocytes in the choroid, ciliary body, or iris. Radiotherapy is the mainstay of therapy for most patients with localized uveal melanoma. Another RT technique used in the treatment of uveal melanomas is charged-particle radiotherapy. Photodynamic therapy is based on the selective destruction of cancer cells or pathological vessels. High-Intensity Focused Ultrasound (HIFU) is a promising technology of thermal destruction of solid tumors located deep under the skin. The principle of operation is based on the heating of a tumor. Sonodynamic therapy (SDT) induces the reactive oxygen species and kills cancer cells. Electroporation applied in vivo delivers drugs or genetic material from the intercellular space to cells. Iontophoresis is a technique in which using electric current increases the biodistribution of drugs in the eyeball. Transcorneal iontophoresis has been shown to increase the local concentration of antibacterial and antifungal drugs, steroids, DNA, and RNA molecules. Theranosticsincorporates diagnostic imaging and therapy. Although no theranostic markers have been developed specifically for uveal melanoma, some NPs have already found use in ophthalmology. UM presents an unmet clinical need. Novel eye-preserving therapeutic approaches for the localized disease are needed.

Die Tumorheterogenität des uvealen Melanoms: Diagnostisch und prognostisch wichtig?

2021 ◽  
pp. 1-3
Author(s):  
Ira Seibel
Keyword(s):  
Uveal Melanoma ◽  
Treatment Strategies ◽  
Intratumoral Heterogeneity ◽  
Correct Prediction ◽  
Patient Counseling ◽  
Clinical Behavior ◽  
Precise Information ◽  
Genetic Features ◽  
Metastatic Risk ◽  
Tumor Biopsies

Tumor biopsies in uveal melanoma (UM) serve mainly the purpose of prognostication and assessment of individual metastatic risk, but can be used for diagnosis in selected cases. The importance of precise information is paramount for selecting adequate surveillance protocols, patient counseling, and optimization of treatment strategies. However, intratumoral heterogeneity and sample representativity are major concerns and can interfere with the correct prediction of the patient’s prognosis. We report a series of cases of UM with distinct morphologically identifiable areas, highlighting the differences in clinical behavior, as well as histopathological and genetic features.

scholarly journals Metastatic Uveal Melanoma: Treatment Strategies and Survival—Results from the Dutch Melanoma Treatment Registry

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1007 ◽  
Author(s):  
Anouk Jochems ◽  
Monique K. van der Kooij ◽  
Marta Fiocco ◽  
Maartje G. Schouwenburg ◽  
Maureen J. Aarts ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Real Life ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Lactate Dehydrogenase Level ◽  
Stage Iv Disease ◽  
Melanoma Treatment

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.

scholarly journals Optimisation of the Chicken Chorioallantoic Membrane Assay in Uveal Melanoma Research

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 13
Author(s):  
Ekaterina A. Sokolenko ◽  
Utta Berchner-Pfannschmidt ◽  
Saskia C. Ting ◽  
Kurt W. Schmid ◽  
Nikolaos E. Bechrakis ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Primary Tumour ◽  
Chorioallantoic Membrane ◽  
Treatment Strategies ◽  
Model Systems ◽  
Treatment Modalities ◽  
In Vivo Model ◽  
Tumour Control ◽  
Angiogenic Potential

The treatment of uveal melanoma and its metastases has not evolved sufficiently over the last decades in comparison to other tumour entities, posing a great challenge in the field of ocular oncology. Despite improvements in the conventional treatment regime and new discoveries about the genetic and molecular background of the primary tumour, effective treatment strategies to either prevent tumours or treat patients with advanced or metastatic disease are still lacking. New therapeutic options are necessary in order to achieve satisfactory local tumour control, reduce the risk of metastasis development, and preserve the eyeball and possibly the visual function of the eye. The development of in vivo model systems remains crucial for the identification and investigation of potential novel treatment modalities. The aim of this study was the optimisation of the chorioallantoic membrane (CAM) model for uveal melanoma research. We analysed the established CAM assay and its modification after the implantation of three-dimensional spheroids. The chorioallantoic membrane of a chick embryo was used to implant uveal melanoma-cell-line-derived spheroids in order to study their growth rate, angiogenic potential, and metastatic capability. Using the UM 92.1, UPMD2, UPMM3, and Mel270 cell lines, we were able to improve the viability of the embryos from 20% to >80% and to achieve up to a fourfold volume increase of the transplanted spheroid masses. The results point to the value of an optimised chicken embryo assay as an in vivo model for testing novel therapies for uveal melanoma by simplifying the research conditions and by contributing to a considerable reduction in animal experiments.

scholarly journals Treatment of uveal melanoma: where are we now?

2018 ◽  
Vol 10 ◽  
pp. 175883401875717 ◽  
Author(s):  
Jessica Yang ◽  
Daniel K. Manson ◽  
Brian P. Marr ◽  
Richard D. Carvajal
Keyword(s):  
Targeted Therapy ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Treatment Strategies ◽  
Current Status ◽  
Primary Therapy ◽  
Disease Outcomes ◽  
Unique Biology ◽  
Disease Biology ◽  
Metastatic Setting

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.

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