Uveal Melanoma

Patient and family cancer history included other BAP1 -TPDS associated cancers, but only three patients had relatives with meningioma. Our findings indicate a need for routine craniospinal imaging in BAP1 -TPDS patients, and surveillance should include patients without family history of meningioma and patients under the age of 30.

AURKA and AURKB are crucial regulators of tumor progression in RB and UM. Aurora kinase inhibition can be explored as a novel therapeutic strategy.

Collectively, our data suggest that erianin serves as an inhibitor of vasculogenic mimicry. Our results unveil a novel therapeutic strategy for combating malignant progression by fine-tuning m5C modification with a natural product.

In this study, our findings show that TRIM2 acts as an m6A-modified substrate of YTHDF3, promoting P53 protein degradation through the ubiquitin-proteasome system. Notably, silencing TRIM2 effectively reduced the tumorigenic effects of YTHDF3 in UVM.

Further, the 15-GEP support vector machine discriminant score predicts small tumors undergoing transformation from low-risk Class 1 to high-risk Class 2 profile. These results shed light on the early genetic evolution of UM and move us closer to a molecular definition of malignant transformation in this cancer type.

Notably, the BET inhibitor mivebresib (ABBV-075) significantly improved survival rates by 50% in a metastatic UM xenograft mouse model and prevented detectable metastases in the bones, spinal cord, and brain...BET and HDAC inhibitors reversed gene expression signatures associated with high metastatic risk and induced a neuron-like phenotype in UM cells. These findings establish BET inhibition as a potent and previously underappreciated vulnerability for metastatic UM.

Both the presence and level of ctDNA at baseline, along with persistence of ctDNA within 3months of treatment-start, are strong negative prognostic markers in mUM. These findings support the clinical utility of ctDNA as a non-invasive tool for disease monitoring.

P2, N=18, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

This pilot study reports on cfDNA methylation signatures that differentiates UM patients from HBDs, and may distinguish between intermediate and high risk UM subgroups, supporting its prognostic potential. However, its role in monitoring disease progression requires further validation. Independent replication studies are warranted to confirm our findings and evaluate the clinical applicability in UM.

This approach, using hyaluronic acid nanoparticle (HANP)-formulated verteporfin (HANP/VP), concurrently induced nuclear- and mitochondrial-DNA damage, promoted immunogenic cell death (ICD), and drove T-lymphocyte infiltration into the tumor microenvironment (TME)...Overall, our findings established HANP/VP as a multifunctional nanomedicine that reprogrammed the TME and elicited potent antitumor immunity through dual DNA damage and STING activation. The study highlights a promising translational strategy for overcoming immunotherapeutic resistance in UM and converting immunologically "cold" tumors into "hot" ones, thereby improving responses to immune checkpoint blockade (ICB).

Our study demonstrates that inherited polymorphisms in IRF4 and HERC2 are independently associated with UM subtype and prognosis, although a SNP-based classifier does not yet outperform the established prognostic model. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Endocytic/signaling proteins exhibit distinct, subtype-linked expression in ocular tumors. Integration with public datasets highlights CAV1 and GIPC1 as adverse survival correlates in UM and positions LRP2/CUBN/DAB2IP dysregulation as features of ocular tumor biology, nominating candidate biomarkers and mechanistic targets.