Tumor Suppressors Condition Differential Responses to the Selective CDK2 Inhibitor BLU-222.

ABSTRACT: Cyclin-dependent kinase 2 (CDK2) inhibitors have recently been developed and have entered clinical trials. Combination approaches can help broaden the use of therapeutic agents and establish more effective treatments. Here, we evaluated the selective CDK2 inhibitor BLU-222 for mechanisms of response in the context of ovarian and breast cancer models. Sensors of cellular CDK activity indicated that sensitivity to either CDK4/6 or CDK2 inhibition was related to the differential dependence on a single CDK for G1-S transition. Unlike CDK4/6 inhibitors, BLU-222 was able to robustly inhibit proliferation through cell-cycle inhibition in both G1 and G2 phases. However, it remained possible for cells to reenter the cell cycle upon drug withdrawal. The antiproliferative strength and impact on G1-S

SUBMITTER: Dommer AP 

PROVIDER: S-EPMC11977231 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature