CCNE1: A Cell Cycle Regulator That Influences Tumor Progression

Cyclin E1 (CCNE1), a pivotal member of the cyclin family, governs the G1/S phase transition of the cell cycle by binding to and activating cyclin-dependent kinase 2 (CDK2), thereby initiating DNA replication and driving S-phase entry. In a broad spectrum of human malignancies-including breast, ovarian, gastric, and non-small cell lung cancers-amplification or overexpression of CCNE1 disrupts the orderly regulation of cell cycle progression, leading to uncontrolled proliferation, impaired DNA damage repair, and genomic instability. These oncogenic consequences are intimately associated with increased tumor aggressiveness, poor patient prognosis, and diminished therapeutic efficacy. This review provides an integrated examination of CCNE1 biology, spanning its physiological regulation in the cell cycle, the molecular mechanisms by which its dysregulation drives tumorigenesis and drug resistance, the clinical implications of CCNE1 amplification as both a prognostic biomarker and a predictor of therapeutic response, and the emerging strategies to target CCNE1-driven vulnerabilities. By synthesizing findings across diverse cancer types and regulatory layers, we evaluate the translational potential of CCNE1 as a diagnostic marker and therapeutic target, and highlight key challenges and opportunities for future investigation.