Conjunctival Melanoma: Current Treatments and Future Options

Grimes, Joseph M.; Shah, Nirav V; Samie, Faramarz H.; Carvajal, Richard D.; Marr, Brian P.

doi:10.1007/s40257-019-00500-3

Cited by 46 publications

(39 citation statements)

References 95 publications

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“…Conjunctival melanoma (CM) is an aggressive neoplasm of the ocular surface. While it is rare, the incidence of this neoplasm is on the rise [1,2]. The annual incidence of CM has been estimated at 0.2 to 0.8 cases per 1,000,000 people, and patient populations particularly susceptible to ultraviolet light damage such as non-Hispanic white men are at the highest risk of developing this malignancy [1,[3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…The annual incidence of CM has been estimated at 0.2 to 0.8 cases per 1,000,000 people, and patient populations particularly susceptible to ultraviolet light damage such as non-Hispanic white men are at the highest risk of developing this malignancy [1,[3][4][5]. CM may arise from primary acquired melanosis (PAM), nevus, or de novo [2,4,5]. While the origins of primary lesions and presenting symptoms vary, patients usually seek care because they notice a pigmented spot on their ocular surface.…”

Section: Introductionmentioning

confidence: 99%

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Structural Protein Analysis of Driver Gene Mutations in Conjunctival Melanoma

Djulbegovic

Uversky

Harbour

et al. 2021

Genes

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In recent years, there has been tremendous enthusiasm with respect to detailing the genetic basis of many neoplasms, including conjunctival melanoma (CM). We aim to analyze five proteins associated with CM, namely BRAF, NRAS, c-KIT, NF1, and PTEN. We evaluated each protein for its intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI) with the Predictor of Natural Disordered Protein Regions (PONDR®) and the Search Tool for the Retrieval of Interacting Genes (STRING®). Our PONDR® analysis found high levels of IDPRs in all five proteins with mutations linked to CM. The highest levels of IDPRs were in BRAF (45.95%), followed by PTEN (31.76%), NF1 (22.19%), c-KIT (21.82%), and NRAS (14.81%). Our STRING analysis found that each of these five proteins had more predicted interactions then expected (p-value < 1.0 × 10−16). Our analysis demonstrates that the mutations linked to CM likely affected IDPRs and possibly altered their highly complex PPIs. Quantifying IDPRs in BRAF, NRAS, c-KIT, NF1, and PTEN and understanding these protein regions are important processes as IDPRs can be possible drug targets for novel targeted therapies for treating CM.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural Protein Analysis of Driver Gene Mutations in Conjunctival Melanoma

Djulbegovic

Uversky

Harbour

et al. 2021

Genes

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“…It represents 2–5% of all eye tumors, 5–7% of melanomas in the ocular region and 0.25% of melanomas overall [ 23 , 24 , 25 , 26 ]. CM shows an incidence of 0.2–0.8 per million in the Caucasian population with rare cases reported in non-Caucasians and its incidence has risen in recent years, most likely due to increased UV exposure [ 27 ]. The mean age of presentation is ~65 years old [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…CM shows an incidence of 0.2–0.8 per million in the Caucasian population with rare cases reported in non-Caucasians and its incidence has risen in recent years, most likely due to increased UV exposure [ 27 ]. The mean age of presentation is ~65 years old [ 26 , 27 ]. CM can arise de novo or originate from primary-acquired melanosis (PAM; also termed conjunctival melanocytic intraepithelial neoplasia (C-MIN) and conjunctival nevi [ 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…ECT is integrated in the therapeutic approach of metastatic cutaneous melanoma, offering an alternative adjuvant option for non-excisable or multiple cutaneous and subcutaneous nodules [ 12 ]. Due to the similarities of CM to cutaneous and mucosal melanomas, the therapies effective in the treatment of these diseases may also show high potency in the management of CM and its metastatic lesions [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Image Analysis of 3D Conjunctival Melanoma Cell Cultures Following Electrochemotherapy

et al. 2020

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Three-dimensional (3D) cell cultures represent small avascular tumors in vitro and simulate some of the biological characteristics of solid tumors, enhancing the evaluation of anticancer drug efficacy. Automated image analysis can be used for the assessment of tumor growth and documentation of changes in the size parameters of 3D tumor spheroids following anticancer treatments such as electrochemotherapy. The objective of this article is to assess the effect of various electroporation (EP) conditions (500–750 Volts/cm, 8–20 pulses, 100 µs pulse duration, 5 Hz repetition rate) combined with different bleomycin concentrations (1–2.5 ug/mL) on normal epithelial (HCjE-Gi) and conjunctival melanoma (CRMM1, CRMM2) 3D-cell cultures, through an automated image analysis and a comparison with standard histological assays. A reduction in tumor mass with loss of cell definition was observed after ECT (750 Volts/cm with eight pulses and 500 Volts/cm with 20 pulses) with bleomycin (1 μg/mL and 2.5 μg/mL) in the histological and immunohistochemical analyses of 3D CRMM1 and CRMM2 spheroids, whereas an increase in volume and a decrease in sphericity was documented in the automated image analysis and 3D visualization of both melanoma cell lines. For all other treatment conditions and for the HCjE-Gi cell line, no significant changes to their morphological features were observed. Image analysis with integrated software tools provides an accessible and comprehensive platform for the preliminary selection of homogenous spheroids and for the monitoring of drug efficacy, implementing the traditional screening methods.

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Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi‐institutional study

et al. 2023

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PurposeMetastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established.Materials and MethodsWe retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022.ResultsOverall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p < 0.001), higher incidence of liver metastases (89% vs. 9%, p<0.001), a lower incidence of lymph nodes metastases (16% vs. 46%, p = 0.043) and a lower incidence of BRAF mutation (0% vs. 55%, p<0.001) compared with patients with conjunctival melanoma (CM). The overall response rate of the first‐line treatment was 18%. Three of the four patients with BRAF‐mutated CM responded to dabrafenib and trametinib treatment. The median progression‐free survival (PFS) and overall survival (OS) of first‐line treatment were 5.1 and 11.9 months, respectively. Among patients with liver metastases, liver‐directed treatment was correlated with better patient PFS (p < 0.001) and OS (p < 0.001) after adjusting for number of metastatic sites and primary sites.ConclusionCM and UM have different characteristics. Patient with CM had a high incidence of BRAF mutation, and the treatment of BRAF and MEK inhibitors conferred clinical benefit. Liver directed therapies had a potential benefit in disease control in patients with liver metastases.

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Conjunctival Melanoma: Current Treatments and Future Options

Cited by 46 publications

References 95 publications

Structural Protein Analysis of Driver Gene Mutations in Conjunctival Melanoma

Structural Protein Analysis of Driver Gene Mutations in Conjunctival Melanoma

Image Analysis of 3D Conjunctival Melanoma Cell Cultures Following Electrochemotherapy

Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi‐institutional study

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