Cell cycle dysregulation, implicated in malignant transformation and tumor progression, occurs in more than 90% of lung cancers, partially due to the aberrant activity of Cyclin-dependent kinases (CDK)–cyclin–RB pathways CDK4 and CDK6 can form complex with D-type cyclins, sequentially phosphorylate the Rb tumor suppressor protein, release E2F1, and thereby facilitate cell cycle progression Inhibiting CDK4/6 impairs cell cycle progression, suppresses tumor cell proliferation, and induces senescence. The gene discussed is E2F1; the disease is lung cancer.