CDK4 and cancer: CDK2 is a protein target of high therapeutic interest due to its role in cell cycle progression and its implication in CyclinE1-mediated resistance to CDK4/6-inhibitor treated cancers (46, 47), but it has historically been challenging to develop CDK2-selective inhibitors, particularly using small molecules, due to the close similarity of CDK2 with other CDK family members, particularly CDK1.