RB1 and cancer: By blocking the formation of the cyclin D-CDK4/6 complexresponsible for the phosphorylation of pRb, the transition of cellcycle from G1 phase to S phase is halted.16 Three small molecule inhibitors of CDK4/6 have been approved bythe FDA for the treatment of multiple cancer types, though toxicityremains a concern.17 The selected P16p,which encompasses the P16-interacting motif with CDK4/6,18,19 has been shown to similarly inhibit pRb phosphorylation and in turnG0/G1 cell cycle progression, resulting in the suppression of cancercell proliferation in both in vitro and in vivo studies.18,20,21