CDK4 and cancer: Since these active kinase complexes were insensitive to the inhibitors specific for CDK4/6, these could cause the resistant phenotype by bypassing CDK4/6 in the cell cycle.1,2 In turn, loss of CDK2 re-sensitized AMBRA1-deficient cancer cells to CDK4/6 inhibition1 emphasizing the need for combined CDK2/4/6 inhibitors (Fig. 1b).