Perspectives for cancer therapies with cdk2 inhibitors

Modern anticancer strategies are designed against specific molecular targets with the goal of sparing normal, non-neoplastic tissues. Choosing specific molecular targets, however, is problematic. Cdk2 (Cyclin dependent kinase 2, cell division kinase 2, p33) is an important candidate target for therapeutic intervention. Phosphorylation of retinoblastoma protein (pRb) by Cdk2 is the penultimate step in the transition from G1 to S phase. Inhibition of this step could potentially result in inhibition of proliferation, cytostasis and possibly apoptosis in human tumors. Cdk2 also plays a critical role in the transition through S phase and the S to G2 transition as well. Inhibitors of the cyclin dependent kinases, such as flavopiridol and UCN-01, are currently in clinical trials. While demonstrating clinical activity, neither acts specifically against Cdk2. Other more specific Cdk2 inhibitors are currently in preclinical development. Further studies to explore the therapeutic worth of such agents are warranted.