CDK4/6
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.
Palbociclib, ribociclib, and abemaciclib with endocrine therapy are first-line standard in HR+/HER2- advanced breast cancer; ribociclib (NATALEE) and abemaciclib (monarchE) are approved in the adjuvant setting. CDK4-selective and CDK2 inhibitors address resistance.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Phosphorylate RB to release E2F and drive G1-S transition; cyclin D1 amplification and RB loss modulate sensitivity.
- 3 · How drugs use it
4 products aim at CDK4/6: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
Phosphorylate RB to release E2F and drive G1-S transition; cyclin D1 amplification and RB loss modulate sensitivity.
- HR+ breast cancer
- Liposarcoma (CDK4 amplification)
- Mantle cell lymphoma
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Sarcomas | >90% | Well-/dedifferentiated liposarcoma CDK4 amplification | Wikipedia | |
| HR-positive / HER2-negative breast cancer | 15-20% | Cyclin D1 (CCND1) amplification | Inhibitors work regardless of amplification | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Abemaciclib was the first CDK4/6 inhibitor approved after surgery for high-risk hormone-positive breast cancer.
A next-generation pill that blocks only CDK4, not CDK6, to keep the benefit of today's drugs without the low blood counts.
Palbociclib was the first CDK4/6 inhibitor (2015), and in 2026 became the first approved as maintenance in HER2-positive, hormone-positive breast cancer.
Ribociclib is the CDK4/6 inhibitor with the most consistent survival benefit, approved for a broad population of early breast cancer patients since 2024.
Ribociclib is a second adjuvant CDK4/6 option, and the only one with data in node-negative stage II disease. Roughly 3 in 100 patients avoid a relapse or death at three years, so the decision depends heavily on individual risk, tolerance of a three-year oral drug, and cost. Whether the benefit persists after treatment ends, as it did with abemaciclib, needs longer follow-up.
Women with hormone-receptor-positive, HER2-negative breast cancer that has spread to lymph nodes and has other high-risk features can now be offered two years of abemaciclib alongside their hormone therapy, with a durable reduction in relapse. It does not apply to node-negative or low-risk disease, and the diarrhoea and cost are real trade-offs to discuss.
Latest papers
topQuery for this target: (TITLE:"CDK4/6" OR ABSTRACT:"CDK4/6" OR TITLE:"CDK4" OR ABSTRACT:"CDK4" OR TITLE:"CDK6" OR ABSTRACT:"CDK6") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CDK4/6, not a curated reading list.
Pages like this
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