CDK4 and neoplasm: Therefore, H3.3K27M represses p16, an endogenous CDK4/6 inhibitor, which suggests that inhibition of CDK4/6 would be a good target to evaluate in H3.3K27M mutant tumor cells, and indeed in in vitro studies we observed that PDGF-B; H3.3K27M; p53-deficient cells are more sensitive than PDGF-B; H3.3WT; p53-deficient cells to CDK4/6 inhibition (32).