CDK4/6 inhibitors
Oral drugs that hold breast cancer cells in the G1 phase of the cell cycle; used with hormone therapy in HR-positive, HER2-negative disease.
What they are
Palbociclib, ribociclib and abemaciclib (suffix «-ciclib») inhibit the cyclin-dependent kinases 4 and 6. They are combined with an aromatase inhibitor or fulvestrant (abemaciclib also alone) for hormone receptor-positive, HER2-negative breast cancer, advanced or high-risk early.
Mechanism of action
Cyclin D binds CDK4 and CDK6, which phosphorylate the retinoblastoma protein (Rb). Phosphorylated Rb releases E2F transcription factors and the cell passes from G1 into S phase. Blocking CDK4/6 keeps Rb active, so the cell stays in G1. Oestrogen drives cyclin D in ER-positive breast cancer, which is why these drugs work best with endocrine therapy.
Target: Cyclin-dependent kinases 4 and 6 (CDK4/6)
Drugs in this class
- PalbociclibThe first CDK4/6 inhibitor: with hormone therapy it holds HR-positive, HER2-negative breast cancer in G1. Main effect…Cyclin-dependent kinases 4 and 6 (CDK4/6)
- RibociclibA CDK4/6 inhibitor for HR-positive, HER2-negative breast cancer, early or advanced, with hormone therapy. It prolongs…Cyclin-dependent kinases 4 and 6 (CDK4/6)
- AbemaciclibA CDK4/6 inhibitor for HR-positive, HER2-negative breast cancer, with hormone therapy or alone. Its hallmark is…Cyclin-dependent kinases 4 and 6 (CDK4/6)
Others in the class
- trilaciclib
Test yourself
Think of the answer, then tap the question to see it.
Which protein stays active when CDK4/6 are blocked, and what does it hold back?
The retinoblastoma protein (Rb), which keeps E2F bound so the cell cannot enter S phase.
In which breast cancer subtype are CDK4/6 inhibitors used?
Hormone receptor-positive, HER2-negative breast cancer, together with endocrine therapy.
Which CDK4/6 inhibitor is known for diarrhoea, and which for QT prolongation?
Abemaciclib for diarrhoea; ribociclib for QT prolongation.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Palbociclib - NCI (National Cancer Institute, 2024).
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Representative model, for educational purposes only.