Ocular Melanoma

The PRAME has significance in discriminating the conjunctival malignant melanoma and pigmented nevus. It is a useful biomarker in the diagnosis of conjunctival malignant melanoma.

Structural analyses of decellularised matrices revealed microarchitecture of differing fibre density and expression differences in collagen 4, collagen 6A1 and nidogen 1, between metastatic risk groups. This approach is a powerful tool for the generation of ECM matrices relevant to high metastatic risk UM.

P1, N=2, Completed, University of Michigan Rogel Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Jul 2024

The in vitro cytotoxicity was accompanied by exposure of DAMPs, suggesting Bel-sar is a potential treatment for CJM by a dual mechanism of action. This dual mechanism may provide a targeted and direct killing of tumor cells and induce an immune response which might decrease local recurrences and metastasis.

The recurrence of a choroidal melanoma is substantiated by the histopathological and molecular analyses, including the finding of a GNA11 mutation. This case exemplifies a remarkably delayed distant recurrence of a choroidal melanoma, which manifested clinically 40 years following enucleation.

P=N/A, N=500, Recruiting, Leiden University Medical Center | N=250 --> 500

This data suggests that DNMT inhibitors cause changes in UM cells that are maintained in cfDNA. The results suggest that targeting methylation in UM treatment and monitoring response to treatment using cfDNA methylation could be a valuable tool.

P=N/A, N=22, Completed, Centre Hospitalier Universitaire de Nice | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Jan 2024

Positive plasma ctDNA reflected the presence of metastases. The ctDNA could be used as a complement or alternative to tissue sequencing. High VAF ctDNA might indicate rapid disease progression in distant metastasis patients.

The present results suggested that hormonal and metabolic dysregulation may be associated with the pathogenesis of SC, and that AR and MCT1 in particular may serve as prognostic indicators and potential therapeutic targets. Additionally, ~10% of SC cases exhibited PD-L1 expression within the druggable range, and these patients are expected to benefit from treatment with immune checkpoint inhibitors.

P2, N=24, Not yet recruiting, Aura Biosciences

In assessing if a CM gene expression panel could aid in the risk stratification of patients with CJM, we found that the uveal melanoma-relevant gene, BAP1, may be important. Additional studies with larger sample sizes are needed to determine the relevance of this and other differentially expressed genes in CJM prognostication.

Although apparently exceedingly rare, epithelioid myxosarcoma should be included as a differential diagnosis for intraocular tumors in cats and they represent a clinical, histologic, and immunohistochemical diagnostic challenge. Early surgical intervention should be considered to prevent local invasion and ascension to the brain.

Anti-PKM2 in the setting of autoimmune retinopathy may be associated with occult pancreatic cancer. The diagnosis of pAIR should be considered and systemic investigation for occult malignancy initiated even in the absence of more commonly associated anti-retinal antibodies.

Tebentafusp, a bispecific T cell engager (TCE) approved for metastatic UM, showed potential in clinical trials, but the objective response rate remains modest...Quantification of predictive power suggested a limited predictive power for single pre-treatment biomarkers, which was improved by early on-treatment biomarkers and combination of predictive biomarkers. Ultimately, this QSP model could facilitate biomarker-guided patient selection, improving clinical trial efficiency and UM treatment outcomes.

None of the carriers of identified variants had familial UM. We identified BRCA1 and MET as genes with pathogenic germline variants in Finnish UM patients, each with a frequency of 0.4% (95% confidence interval, 0-2).

Drug screening using mitomycin-C (MMC), 5-fluorouricil (5-FU), and 6-Diazo-5-oxo-L-norleucine (DON) were performed...Ocular adnexal SebCA cell lines can be established using conditional reprogramming cell conditions, and our three new models are useful for testing therapies and interrogating the functional role of MYC and other possible molecular drivers. Current topical chemotherapies promote both apoptosis and differentiation in SebCA cells, and these tumors appear sensitive to inhibition or MYC-associated metabolic changes.

Checking tumor markers in the aqueous humor can aid in diagnosis, and aggressive treatment of metastatic iris tumors must help maintain patients' Quality of Life.

These results suggest that patient phenotypes are associated with the inherent characteristics of germline RB1 variants. These findings indicate the potential application of genetic testing results in clinical practice.

We were able to successfully conduct NGS studies in paraffin-embedded material archived for 10 years using both middlesized (OPA) and large (OCA v3) NGS panels. The identified S3FB1 mutation helps to explain the onset of metastases, even though the patient had spindle cell predominant UM with BAP-1 preservation, which are normally associated with decreased metastases risk. Our case highlights the value of using large NGS panels to unravel the molecular landscape of UM and further understand this unique eye cancer.

It is advocated that for patients presenting with cataracts, attention should be paid to the possibility of intraocular tumors. Meticulous slit-lamp microscopy may reveal a reflection of the surface of a malignant melanoma, preventing misdiagnosis.

Our results showed that bevacizumab inhibited MP41 cell proliferation and had an additive effect when administered with RT. In conclusion, our study offers a different perspective on the treatment of uveal melanoma, and these results, when supported by animal experiments and clinical studies in the future, might be a new step in the treatment of this challenging ocular tumor.

The drug belzutifan shows great promise for controlling RHs and preventing vision loss in patients with VHL. Further work needs to address the optimal dose, role of the drug as a neoadjuvant therapy, and long-term efficacy and tolerability of the drug in a larger cohort of patients with ocular tumors.

In vitro tests on MP41 (BAP1 positive) and MP46 (BAP1 negative) cancer cell lines using inhibitors pamiparib (PARP1) and Ymu1 (DTYMK) demonstrated significant cytotoxic effects...Our hypothesis of the double hit into tumoral DNA metabolism as a possible therapeutic option in uveal melanoma was confirmed since combined targeting of DTYMK and PARP1 affected all tested cytophysiological parameters with the highest efficiency. Our in vitro findings provide insights into novel therapeutic avenues for managing uveal melanoma, warranting further exploration in preclinical and clinical settings.

P2, N=37, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> Jul 2026 | Trial primary completion date: Dec 2024 --> Jul 2026

P2, N=22, Completed, Aura Biosciences | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Apr 2024

Cardiac autopsy from one patient confirmed immune-related myocarditis, and immunosequencing revealed expansion of a single T-cell clone that was not present in the pretreatment tumor. These cases highlight the importance of understanding risk factors that may contribute to immune-related myocarditis and other severe immune-related adverse events when CD28 agonism is targeted in the context of checkpoint inhibition.NEON-2 (NCT04920383).

The ultrasound images of ovarian collision tumor have certain specificity, but diagnosis by preoperative ultrasound is difficult. The combination of epithelial and mesenchymal cell tumors is one of the most common types of ovarian collision tumor. The O-RADS score of ovarian collision tumor is mostly ≥ 4, which can sensitively detect malignant tumors.

Davoceticept was generally well tolerated as monotherapy at intravenous doses up to 10 mg/kg. Evidence of clinical activity was observed with davoceticept monotherapy and davoceticept in combination with pembrolizumab, notably in RCC. However, two fatal cardiac events occurred with the combination of low-dose davoceticept and pembrolizumab. Future clinical investigation with davoceticept should not consider combination with programmed death-1-inhibitor anticancer mechanisms, until its safety profile is more fully elucidated.

Ipilimumab and nivolumab are ICIs targeting the cytotoxic T-lymphocyte-associated antigen-4 and the programmed-cell death protein-1, respectively. Herein, we present a case of choroidal melanoma having liver metastasis treated with nivolumab and ipilimumab and transarterial radioembolization, achieving a 3-year survival.

The severity of liver metastasis was related to the hepatic metastatic origin and chromosome 8 abnormalities rather than monosomy 3 and BAP1 deficiency. The presented CAM xenograft model may prove useful to study the metastatic potential of patients or to test individualized therapeutic options for metastasis in different organs.

P1, N=20, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2025

Treatment options are limited to Tebentafusp in patients with HLA-A*02:01 mutation with immunotherapy and chemotherapy yielding poor results...In a recent phase I trial of a PRMT5 inhibitor, PRT811, clinical activity was described in cases of CAUM. 676 CAUM and 9666 CASM patients underwent hybrid capture based CGP to evaluate genomic alterations (GA)... Although MTAP loss is less frequent in CAUM than in CASM, the recent evidence that this genomic alteration predicts responsiveness to PRMT5 inhibition is noteworthy. This highlights the importance of further investigating this biomarker for patients with this rare and clinically aggressive type of cancer.

P=N/A, N=40, Recruiting, Duke University | Not yet recruiting --> Recruiting

P1/2, N=22, Completed, Craig L Slingluff, Jr | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Mar 2024 | Trial primary completion date: Sep 2024 --> Mar 2024

Although type I IFNs cause direct toxicity on corneal cells, they do not induce significant side effects on the healthy ocular surface. Considering its therapeutic and preventive effects, topical type I IFN is safe and effective for treating ocular surface tumors. The potential for ocular side effects should be considered in eyes with identified risk factors.

Pediatric autoimmune retinopathy and optic neuropathy are rare diseases that can present with unique signs and symptoms. In pediatric patients who present with symptoms of subacute progressive vision loss with negative inflammatory workups, a history of prior neoplasm, and/or clinical findings of progressive retinopathy or optic neuropathy, an autoimmune process should be considered in the differential.

The tumor cells were positive for SOX10, Melan A, S100 and HMB45. We herein propose a novel variant of conjunctival melanoma with rich vascularization, clinically causing persistent bleeding.

VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

Biological experiments were performed and demonstrated that the silencing of RBMS1 inhibited ocular melanoma proliferation and promoted apoptosis. Our study highlighted that RBMS1 reflects a distinct microenvironment and promotes tumor progression in ocular melanoma, contributing to the therapeutic customization and clinical decision-making.

Furthermore, the disease-free survival rate was increased in the groups with low expression of TP53I11, SH2D5, and SEMA5A. JQ-1 may act downstream of BRD4 and suppress ocular melanoma growth by inducing G1 cell cycle arrest.

This study provides an undesirable insight of senescent endothelial cells in promoting UM metastasis.