Our finding on the repression of SIRT6 transcription by E2F1 will broaden the therapeutic opportunities to enhance SIRT6 tumor suppressor activities with compounds like CDK4/6 inhibitor, which retains E2F1 in the RB-E2F1 complex by diminishing the phosphorylation of RB by CDK4/6. The gene discussed is SIRT6; the disease is neoplasm.