CDKN2A and non-small cell lung carcinoma: First, since hypermethylation of CDKN2A with loss of p16 expression is the common mechanism to activate CDK4/6 in NSCLC [4, 28], we tested decitabine, a potent demethylating agent that can efficiently induce p16 protein expression to block CDK4/6 activity independently of exposure to palbociclib [4].