Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies

Dysregulation of the cell cycle is one of the fundamental mechanisms underlying tumorigenesis, making cell cycle-related regulators potential antitumor therapeutic targets. Despite significant advances in understanding cell cycle regulatory networks, there is still a lack of a comprehensive and up-to-date synthesis that integrates the latest mechanistic insights with their translational potential in oncology. This review first systematically outlines the pivotal role of the cyclin-cyclin-dependent kinase (CDK)-cyclin-dependent kinase inhibitor (CKI) axis in driving aberrant cell cycle progression in tumors. Then the complex regulatory mechanisms of the tumor cell cycle were explored from various perspectives, including transcriptional control, post-translational modifications, checkpoint mechanisms, crosstalk with cellular processes, and integration with key signaling pathways. Furthermore, we highlight a series of clinically relevant biomarkers tightly linked to cell cycle dysregulation. Focusing on approved therapeutic agents and natural compounds in clinical trials, current treatment approaches that target the cell cycle and related metabolic pathways were also comprehensively assessed, and their prospects in precision oncology were elaborated. Finally, we discuss persistent challenges, including the incomplete understanding of tumor-specific cell cycle networks and the barriers to the clinical translation of targeted therapies. We advocate for future research to leverage multi-omics integration and systems biology approaches to facilitate more precise and effective cell cycle-directed interventions. This work offers a comprehensive framework that connects the fundamental mechanisms of cell cycle dysregulation in tumors with clinical translation, aiming to accelerate biomarker discovery and the development of next-generation precision oncology strategies.