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The ordered sequence a cell goes through to copy its DNA and split in two, with checkpoints along the way where it pauses to check for damage. Cancer cells run through the checkpoints.
The phases are G1 (growth), S (DNA copying), G2 (checking) and M (mitosis, the actual division); proteins called cyclins and cyclin-dependent kinases (CDKs) drive the transitions, and tumour suppressors such as RB1 and p53 hold them back until conditions are right. Cancers accelerate the cycle by amplifying cyclin D or losing RB1 and p53, and many drugs act on it: CDK4/6 inhibitors (palbociclib, ribociclib) hold the cell at the G1 checkpoint, while taxanes and vinca alkaloids sabotage mitosis itself. The 'cell-cycle checkpoint' is unrelated to the 'immune checkpoint' of immunotherapy, despite the shared word.
In plain words · CDK4/6 is the engine that pushes a cell to copy its DNA. Blocking it alongside hormone therapy roughly doubled the time hormone-driven breast cancer stays controlled.
Showing the target this term concerns: CDK4/6.
Why small-cell lung cancer has no targeted therapy in the conventional sense: it is built from the loss of TP53 and RB1, and the drugs that transformed non-small-cell disease inhibit gains rather than restore losses. The NOTCH result pointed at DLL3 and, eventually, at tarlatamab.
This review is the textbook basis for the cyclin D-CDK4/6-RB axis that palbociclib, ribociclib and abemaciclib target in breast cancer, and for reading CDKN2A loss and cyclin D1 amplification in tumour genomes.
This review fixed the picture of p53 as the guardian of the genome that every textbook uses. It explains why TP53-mutant cancers are aggressive and hard to treat, why MDM2 inhibitors are being developed to reactivate wild-type p53, and why germline TP53 testing matters in families.
This paper closed the loop between DNA damage, p53 and the cell cycle machinery. p21 is now a standard marker of p53 activity, part of how chemotherapy and radiotherapy stop cells dividing, and a component of the senescence response that CDK4/6 inhibitors exploit.
Shares Ribociclib, Abemaciclib, Palbociclib, CDK4/6 inhibitors.
Shares Sherr and Roberts 1999: CDK inhibitors as regulators of the G1 phase, El-Deiry 1993: WAF1, the gene through which p53 stops cell division, WEE1, Ribociclib.
Shares Ribociclib, Abemaciclib, Palbociclib, CDK4/6 inhibitors.
Shares Tumour suppressor gene, CDK4/6, CDK4/6 inhibitors, p53 / RB / cell-cycle checkpoint.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, Tumour suppressor gene, TP53.
Shares Ribociclib, Abemaciclib, CDK4/6, Palbociclib.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, Tumour suppressor gene, p53 / RB / cell-cycle checkpoint, TP53.
Shares Ribociclib, Abemaciclib, Palbociclib.