Uveal Melanoma

P2, N=85, Active, not recruiting, iOnctura | Recruiting --> Active, not recruiting

P=N/A, N=108, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

Disruption of redox equilibrium by enhancing reactive oxygen species (ROS) via a mitochondria-targeted oxidative phosphorylation inhibitor triggered endoplasmic reticulum stress and downregulated SPP1 expression, thereby defining a direct metabolic-immune regulatory axis. Together, our findings reveal a previously unrecognized ROS-SPP1-CD44 axis that links tumor redox homeostasis to immune evasion, providing mechanistic insight into the immune-resistant phenotype of UM and suggesting potential therapeutic vulnerabilities within the metabolic-immune crosstalk.

The PIEZO1-DOT1L axis mediated ECM stiffness-driven stemness and tumor progression in UM. Targeting this mechanotransduction pathway by modulating ECM stiffness or its downstream effectors may provide a novel therapeutic strategy for UM.

LP-WGS appears feasible for SCNAs detection in FFPE uveal melanoma specimens, including cases previously treated before enucleation, and holds promise to inform prognostic stratification in this rare tumor type. The successful application of LP-WGS to FFPE uveal melanoma specimens supports prospective investigations in rare cancers and may enable the development of personalized treatment strategies.

This study establishes and validates a seven-gene signature associated with metastasis and prognosis in UVM. The findings provide a framework for understanding molecular determinants of tumor progression and immune microenvironment alterations, and may offer guidance for future mechanistic studies and therapeutic exploration.

Rescue experiments further confirmed these interactions, contributing to a comprehensive understanding of the NEAT1/miR-506-3p/STAT3 axis in UM. The NEAT1/miR-506-3p/STAT3 axis has emerged as a promising diagnostic and therapeutic target for UM, providing a novel perspective on the pathogenesis of this challenging malignancy.

To understand this, we generated human embryonic stem cells that stably express doxycycline inducible BAP1 shRNAs...Thus, our results demonstrate that the knockdown of histone H2A deubiquitinase BAP1 restricts the lineage specification ability of human embryonic stem cells to a large extent, while it does not affect their undifferentiated state. Our results have implication in the study of early human development as well as cancer biology.

These findings indicate that ferroptosis dysregulation is a hallmark of aggressive UM. SLC7A11, GPX4, and TFR1 represent clinically relevant biomarkers and potential therapeutic targets.

In conclusion, our results highlight that a subset of EPHs and EFNs may be associated with worse clinical outcomes (EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2), and an aggressive histological subtype (EPHA2, EPHA4, EPHA8, EPHB4, EFNA1, EFNA3, EFNA4, and EFNB2). The potential correlation of these genes with clinicopathological parameters of UVM need to be evaluated and validated with bioinformatic and experimental approaches in well-characterized cohorts of UVM patients.

This is the first study to provide consensus-based guidance incorporating GEP and PRAME status into surveillance recommendations for uveal melanoma, offering a standardized framework to guide clinical practice and future research.

These findings support the adaptability of UVM lesions and suggest rational combination therapies targeting both primary GNAQ/GNA11-driven oncogenic signals and their compensatory networks as a more effective, personalized treatment approach for advanced UVM.