RBX1 loss sensitizes tubo-ovarian, high-grade serous ovarian cells to CDK2 inhibition by SNS-032 (opens in new tab)

Tubo-ovarian, high-grade serous carcinoma (HGSC) is the most lethal gynecological malignancy, with limited targeted therapies and poor outcomes. Heterozygous loss of RBX1 occurs in approximately 81% of HGSCs and drives chromosome instability and cellular transformation. Here, we identify CDK2 as a novel synthetic lethal (SL) interactor of RBX1 in clinically relevant RBX1+/− fallopian tube secretory epithelial cell models. Genetic silencing or pharmacologic inhibition of CDK2 with siRNA duplex...