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

• Published in: Folia biologica Vol. 69; no. 5-6; pp. 194 - 196
• Main Author: Macůrek, Libor
• Format: Journal Article
• Language: English
• Published: Czech Republic Charles University in Prague, First Faculty of Medicine 01-01-2023
• Subjects: Anaphase; Anaphase-promoting complex; Breast cancer; Breast Neoplasms - drug therapy; Cancer therapies; Cell Cycle; Cell division; Cell growth; Cell proliferation; Cell size; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - metabolism; Cyclin-Dependent Kinase 6 - metabolism; Cyclin-dependent kinases; DNA biosynthesis; DNA damage; Endoplasmic reticulum; Epidermal growth factor; ErbB-2 protein; Female; Histone H2A; Homeostasis; Humans; Kinases; MAP kinase; p53 Protein; Protein Kinase Inhibitors - pharmacology; Proteins; Proteomes; Proteomics; Rapamycin; Retinoblastoma; Retinoblastoma-associated protein; Senescence; TOR protein; Czech Republic; senescence; cell growth; cyclin-dependent kinase; cell cycle; CDK4/6 inhibitor
• ISSN: 0015-5500; 2533-7602
• DOI: 10.14712/fb2023069050194

Cyclin-dependent kinases (CDKs) are master regulators of proliferation, and therefore they represent attractive targets for cancer therapy. Deve-lopment 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.