Fol. Biol. 2023, 69, 194-196

Many Ways to the Cell Cycle Exit after Inhibition of CDK4/6

Libor Macůrek

Laboratory of Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

Received December 2023
Accepted December 2023

Cyclin-dependent kinases (CDKs) are master regulators of proliferation, and therefore they represent attractive targets for cancer therapy. Deve­lopment of selective CDK4/6 inhibitors including palbociclib revolutionized the treatment of advanced HR+/HER2 breast cancer. Inhibition of CDK4/6 leads to cell cycle arrest in G0/G1 phase and eventually to a permanent cell cycle exit called senescence. One of the main features of the senescence is an increased cell size. For many years, it was believed that the non-dividing cells simply continue to grow and as a result, they become excessively large. There is now emerging evidence that the increased cell size is a cause rather than consequence of the cell cycle arrest. This review aims to summarize recent advances in our understanding of senescence induction, in particular that resulting from treatment with CDK4/6 inhibitors.


This study was supported by the Ministry of Health of the Czech Republic (NU22-03-00276).


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