Category: signaling
Sequential phosphorylation events drive G1 → S → G2 → M progression. Cyclin D + CDK4/6 phosphorylate Rb → releases E2F → S-phase entry. Cyclin E + CDK2 in late G1. Cyclin A + CDK2/1 in S/G2. Cyclin B + CDK1 in mitosis. p53 / p21 / p16 are major brakes. CDK4/6 INHIBITORS (palbociclib, ribociclib, abemaciclib) block G1 → S in HR+/HER2− metastatic breast cancer — synergistic with aromatase inhibitors or fulvestrant. AURORA + PLK1 kinases coordinate mitosis. Chemotherapy targets: taxanes stabilize microtubules (M); vinca alkaloids depolymerize (M); 5-FU / methotrexate hit S; etoposide blocks topo II in G2/M.