Targeting USP8 causes synthetic lethality through degradation of FGFR2 in ARID1A-deficient ovarian clear cell carcinoma.

ABSTRACT: Over half of ovarian clear cell carcinoma (OCCC) cases exhibit deficiencies in the ARID1A gene, a chromatin remodeling complex component. OCCC is resistant to chemotherapy and challenging to treat, necessitating new drug treatment strategies. This study used a publicly available dependency factor database to identify synthetic lethal targets for ARID1A-deficient cancer. The DepMap portal was used to identify genes on which ARID1A-deficient cancer cell lines are highly dependent. Our analysis limited to ovarian cancer cell lines only identified the deubiquitinating enzyme USP8 as a synthetic lethal target in ARID1A-deficient OCCC cancer cell lines and mouse xenograft models. In addition, USP8 inhibitors were more selective for ARID1A-deficient cells than existing candidate drugs used in pro

SUBMITTER: Saito R 

PROVIDER: S-EPMC11903656 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature