Identification of targetable epigenetic vulnerabilities for uveal melanoma.

ABSTRACT: Uveal melanoma (UM) is the most common adult primary intraocular malignancy, with a strong predilection for hepatic metastasis, occurring in approximately 50% of cases. Metastatic UM is highly resistant to therapy and is almost invariably fatal. The strongest genetic driver of UM metastasis is loss of function of the tumor suppressor BRCA-associated protein 1 (BAP1), which leads to widespread epigenetic dysregulation. To identify novel therapeutic strategies, we investigated whether targeting the epigenome of UM could reveal new vulnerabilities. We performed a high-throughput compound screen using a curated epigenetic inhibitor library and identified BET (bromodomain and extra-terminal domain) inhibition as a particularly promising approach. While previous clinical trials with BET inhibito

SUBMITTER: Yenisehirli G 

PROVIDER: S-EPMC12830624 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature