Targeting CDK2 in cancer: challenges and opportunities for therapy

[Display omitted] •CDK2 has key roles in cell cycle, DNA replication and DNA damage.•Multiple biomarkers can indicate increased CDK2 activity.•Some cancers have particular susceptibility to CDK2 inhibition.•The development of selective CDK2 inhibitors is challenging. Cyclin-dependent kinase 2 (CDK2) plays a pivotal part in cell cycle regulation and is involved in a range of biological processes. CDK2 interacts with and phosphorylates proteins in pathways such as DNA damage, intracellular transport, protein degradation, signal transduction, DNA and RNA metabolism and translation. CDK2 and its regulatory subunits are deregulated in many human cancers and there is emerging evidence suggesting CDK2 inhibition elicits antitumor activity in a subset of tumors with defined genetic features. Previous CDK2 inhibitors were nonspecific and limited by off-target effects. The development of new-generation CDK2 inhibitors represents a therapeutic opportunity for CDK2-dependent cancers.