G1 phase cell cycle arrest (G1 arrest)

G1 phase cell cycle arrest is a physiological state in which a cell stops progressing through the cell cycle before the commencement of DNA synthesis (S phase). It is not a single molecular target but rather a complex biological outcome regulated by various proteins, most notably the Cyclin-Dependent Kinases (CDK4 and CDK6) and their regulatory partners, the D-type cyclins. In healthy cells, G1 arrest serves as a critical checkpoint to ensure that DNA is undamaged and that the environment is favorable for division (StatPearls, 2023). In the context of oncology, inducing G1 phase arrest is a major therapeutic strategy used to halt the uncontrolled proliferation of cancer cells. Drugs such as Palbociclib and Abemaciclib specifically target the CDK4/6-Cyclin D complex to prevent the phosphorylation of the Retinoblastoma (Rb) protein, effectively locking the cell in the G1 phase and preventing tumor growth (NCBI/PubMed, 2021). While highly effective in hormone receptor-positive breast cancers, the induction of cell cycle arrest can also affect non-cancerous hematopoietic cells, leading to common side effects like neutropenia (National Cancer Institute, 2022).

Other names

G1/S checkpoint arrestG1-phase growth arrestCell cycle arrest at G1 phase

Induction of G1 phase arrest is typically achieved through the inhibition of Cyclin-Dependent Kinases (CDK4/6), which prevents the phosphorylation of the Retinoblastoma (Rb) protein, thereby blocking the transition from G1 to S phase.