The rationale for investigating the glucose metabolic reprogramming associated with resistance to palbociclib is also supported by preclinical studies showing that (i) CDK4/6 inhibition enhances central carbon metabolism, the number of mitochondria and reactive oxygen species (ROS) production, a phenomenon associated with enhanced mTORC1 activity in pancreatic cancer models [17] and that (ii) CDK4/6 inhibitors efficacy is potentiated by autophagy inhibition in Rb-positive solid tumors [9]. This evidence concerns the gene RB1 and pancreatic neoplasm.