Current and emerging treatment options for uveal melanoma

Pereira, Patrícia M. R.; Odashiro, Alexandre Nakao; Lim, Li–Anne S; Miyamoto, Cristina; Blanco, Paula; Odashiro, Maçanori; Maloney, Shawn C.; Souza, Dominique Fausto de; Burnier, Miguel N.

doi:10.2147/opth.s28863

Cited by 71 publications

(91 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[24][25][26] In many types of cancer, epigenetic mechanisms controlling gene expression have become therapeutic targets. Other investigators have explored the use of epigenetic mechanisms of disease control in uveal melanoma through inhibiting histone deacetylation using FDA-approved agents with promising results, and vorinostat, a histone deacetylation inhibitor, is in phase 2 studies.…”

Section: Discussionmentioning

confidence: 99%

The Demethylating Agent 5-Aza Reduces the Growth, Invasiveness, and Clonogenicity of Uveal and Cutaneous Melanoma

Rajaii

Asnaghi

Enke

et al. 2014

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Rajaii F, Asnaghi L, Enke R, Merbs SL, Handa JT, Eberhart CG. The demethylating agent 5-Aza reduces the growth, invasiveness, and clonogenicity of uveal and cutaneous melanoma. Invest Ophthalmol Vis Sci. 2014;55:6178-6186. DOI:10.1167/ iovs.14-13933 PURPOSE. Uveal melanoma is the most common primary intraocular malignancy in adults. Although local disease can be controlled with radiation therapy or enucleation, many cases are complicated by metastases, which account for the significant mortality from this disease. To date, no chemotherapeutic regimens effectively treat local or metastatic disease. Epigenetic silencing of tumor suppressor genes has been shown to be an important factor in the growth and metastasis of many cancers. One form of epigenetic alteration is DNA methylation, which often occurs at promoter elements resulting in the silencing of target gene transcription. METHODS. We used 5-aza-20 -deoxycytidine (5-Aza), a well characterized demethylating agent that is US Food and Drug Administration approved to decrease DNA methylation in multiple uveal and cutaneous melanoma cell lines.RESULTS. Demethylation of melanoma cell lines using 5-Aza causes significant decreases in growth, invasion, and clonogenicity. Treatment of melanoma cells with combined 5-Aza therapy and irradiation showed an even more pronounced effect on cell viability. In addition, treatment with 5-Aza decreased the number of metastases from the eye to the lung in a murine cutaneous melanoma xenograft model. CONCLUSIONS.We demonstrate in vitro and in vivo that demethylating agents such as 5-Aza may be promising chemotherapeutic agents for treating melanoma and decreasing progression to metastatic disease. These results provide proof of concept for an exciting potential therapy to reduce mortality from this disease. Future work will focus on identifying pathways that mediate these changes.Keywords: demethylation, epigenetics, melanoma, metastasis, uveal melanoma U veal melanoma is the most common primary intraocular malignancy in adults, with an age-adjusted incidence of 5.1 cases per million.1 Advances in local therapy have allowed preservation of the patient's eye and vision in many cases; however, the 5-year survival rate of 81.6% has remained unchanged from 1976 to 2008, underscoring the need to develop effective therapies for this deadly disease. 1 Epigenetic mechanisms controlling gene expression have long been known to have a role in cancer development. [2][3][4] Changes in DNA methylation serve as early markers of tumor formation, and DNA methylation at CpG islands in promoters has been shown to decrease expression of tumor suppressor genes in many malignancies, including uveal melanoma. 5,6 In addition, demethylating agents have been used to decrease tumor formation in animal models of cancer and are US Food and Drug Administration (FDA) approved as treatment of myelodysplastic syndrome.7 However, the functional effects of altered DNA methylation in uveal melanoma are unclear.To determine the role of DNA methylatio...

show abstract

Section: Discussionmentioning

confidence: 99%

The Demethylating Agent 5-Aza Reduces the Growth, Invasiveness, and Clonogenicity of Uveal and Cutaneous Melanoma

Rajaii

Asnaghi

Enke

et al. 2014

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…Advances over the past few decades have given us powerful tools for controlling uveal melanoma locally and preventing enucleation; however, we have yet to develop an effective treatment to reduce the risk of metastatic disease or to effectively treat it when it occurs [1][2][3]. Waiting for growth to occur in small lesions identified as high risk by an ophthalmologist can increase the risk of metastasis even when controlling for tumor size (relative risk of 8 controlling for tumor size) [4,5].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling as an Adjunctive Measure to Guide the Management of Indeterminate, High-Risk Choroidal Melanocytic Lesions: A Pilot Study

et al. 2018

View full text Add to dashboard Cite

Purpose: To describe our early experience with gene expression profiling (GEP) assessment for juxtafoveal, subfoveal, and peripapillary indeterminate high-risk melanocytic lesions to assist in making early treatment decisions in patients who did not feel comfortable with either close observation or definitive treatment. Methods: A prospective cohort of patients with indeterminate lesions who underwent GEP were enrolled. Nonparametric statistical analysis was utilized given the small sample size. Results: Fifteen patients were included in this series. Six (40%) were class 1A and 9 (60%) class 1B. Class 1A and 1B lesions had a median of three and four clinical risk factors, respectively (p = 0.27). There was no statistically significant difference for the largest basal diameter between the classes (p = 0.31); however, class 1B lesions were thicker than class 1A lesions (p = 0.03). None of the class 1A lesions showed definite growth or metastasis over a mean follow-up period of 17.1 ± 1.8 months from fine needle aspiration biopsy. All class 1B patients opted for plaque brachytherapy, and to date none of these patients have developed metastasis, with a mean follow-up of 18.7 ± 8.4 months. Conclusion: There may be a role for GEP assessment in high-risk, indeterminate, posteriorly located choroidal lesions to assist in treatment planning.

show abstract

“…The vast majority of these affect the choroid, the pigmented, highly vascular layer of the eye between the sclera and the retina (1). Uveal melanomas are rare, with a mean age-adjusted incidence of 5.1 per million in the United States per year, but are sight-and life-threatening (2,3). The case-fatality rate for uveal melanoma is approximately 50%, with most deaths due to liver metastases (4).…”

Section: Introductionmentioning

confidence: 99%

Eye Cancer Incidence in U.S. States and Access to Fluoridated Water

Schwartz

2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Environmental risk factors for uveal melanomas (cancer of the iris, ciliary body, and choroid) have not been identified. To search for these, we examined the correlation of age-adjusted eye cancer incidence rates, a surrogate for uveal melanoma rates, in U.S. states with group level geographic and demographic factors using multivariate linear regression. Incidence rates for eye cancer were inversely correlated with the percentage of the population receiving fluoridated water; that is, higher rates were found in states with lower prevalences of fluoridation (P ¼ 0.01). Fluoride is known to inhibit the growth of microbial agents that cause choroiditis and choroidal lesions in animals. We speculate that fluoridation protects against choroidal melanoma by inhibiting microbial agents that cause choroiditis and/or choroidal lesions in humans. Cancer Epidemiol Biomarkers Prev; 23(9); 1707-11. Ó2014 AACR.

show abstract

Current and emerging treatment options for uveal melanoma

Cited by 71 publications

References 120 publications

The Demethylating Agent 5-Aza Reduces the Growth, Invasiveness, and Clonogenicity of Uveal and Cutaneous Melanoma

The Demethylating Agent 5-Aza Reduces the Growth, Invasiveness, and Clonogenicity of Uveal and Cutaneous Melanoma

Gene Expression Profiling as an Adjunctive Measure to Guide the Management of Indeterminate, High-Risk Choroidal Melanocytic Lesions: A Pilot Study

Eye Cancer Incidence in U.S. States and Access to Fluoridated Water

Contact Info

Product

Resources

About