By blocking CDK4/6, palbociclib has been shown to inhibit Rb phosphorylation when combined with letrozole in ER-positive breast cancer xenografts, with the combination reducing Rb phosphorylation, and resultant downstream signaling and tumor growth, to a greater extent than either agent alone (Figure 1; Pfizer Inc., 2016). The gene discussed is RB1; the disease is neoplasm.