Involvement of cyclins in the pathogenesis of cancer.

BACKGROUND: Cyclins are fundamental regulators of the eukaryotic cell cycle, orchestrating cell cycle transitions through their interactions with cyclin-dependent kinases (CDKs). Aberrant expression or activation of cyclins disrupts normal cell cycle control, leading to uncontrolled proliferation, genomic instability, and tumorigenesis. Overexpression of specific cyclins has been documented in multiple malignancies, notably breast cancer, underscoring their oncogenic potential. Despite extensive research, the context-dependent roles of cyclins, their isoform-specific functions, and mechanisms underlying resistance to cyclin-targeted therapies remain incompletely understood.

AIM OF THE REVIEW: This review aims to provide an updated and comprehensive overview of the molecular mechanisms by which cyclins contribute to cancer initiation and progression. It also explores recent advances in therapeutic interventions targeting cyclins and CDK signaling pathways, highlighting both the promise and limitations of current cyclin-directed strategies.

KEY SCIENTIFIC CONCEPTS OF THE REVIEW: We systematically analyzed relevant literature retrieved from PubMed and Google Scholar using keywords such as "cyclins," "cyclin-dependent kinases (CDKs)," "cell cycle," and "CDK inhibitors." The review discusses the multifaceted roles of cyclins in promoting oncogenic transformation and therapeutic resistance, emphasizing the importance of cellular context in determining their biological effects. Furthermore, it evaluates novel approaches to overcome resistance to CDK4/6 inhibitors and the potential of cyclin-based therapeutic targeting to improve cancer management and patient outcomes. A deeper understanding of cyclin biology may facilitate the development of precision strategies against cancer metastasis and progression.