Academia Sinica Logo

Cases of ovarian clear cell carcinomas (OCCC) with wild-type ARID1A gene are chemo-resistant and currently lack specific therapies. We identified circadian gene BMAL2 as a critical oncogene that promotes OCCC tumorigenesis by preventing endogenous DNA damage.

BMAL2 depletion suppressed expression of homologous recombination DNA repair genes, including RAD51, leading to accumulated DNA double-stranded breaks, 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 and facilitated BMAL2 degradation. GW833972A is effective by itself at a high dose and can also be used at lower dosages to enhance the effectiveness of PARP inhibitor to suppress OCCC tumor growth. Together, our findings reveal an essential oncogenic role of BMAL2 and demonstrate that it is an appealing therapeutic target for OCCC.

The study was led by Dr. Wendy W. Hwang-Verslues from the GRC, AS with PhD student Grace Y. T. Tan from TIGP-MCB, AS/NDMU, as first author. Supported by AS and the NSTC, the findings were published in EMBO Molecular Medicine on April 3, 2026.