BMAL2 is a druggable target for ovarian clear cell carcinoma (OCCC)

ABSTRACT: Ovarian clear cell carcinomas (OCCC), particularly cases that retain wild-type ARID1A expression, are chemoresistant and lack specific therapies. We identified BMAL2 as a critical oncogene that promotes OCCC tumorigenesis by preventing endogenous DNA damage. BMAL2 depletion altered expression of genes encoding DNA damage repair proteins, including RAD51, a core enzyme of the homologous recombination pathway. This led to DNA double-stranded break accumulation, decreased cell viability and reduced tumor growth. This dependence on BMAL2 to maintain DNA integrity and cell viability can be a new route to suppress OCCC. Consistent with this idea, we found that small molecule GW833972A bound BMAL2 with high affinity and facilitated its degradation. This in turn reduced RAD51 expression, leading t

SUBMITTER: Grace, Y.T. Tan 

PROVIDER: S-SCDT-10_1038-S44321-026-00414-8 | biostudies-other |

REPOSITORIES: biostudies-other