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# 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.

Updated Nov 1, 2026

## 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)

## Key points

- Indication: HR-positive, HER2-negative breast cancer, always paired with endocrine therapy (abemaciclib can also be used alone).
- Neutropenia is the main toxicity of palbociclib and ribociclib: blood counts are checked regularly.
- Abemaciclib: diarrhoea is the signature effect.
- Ribociclib: QT prolongation, so ECG and electrolytes are checked.
- All are CYP3A substrates: avoid strong inhibitors, inducers and grapefruit.

## Drugs in this class

- [**Palbociclib** The 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)](https://durgical.com/en/pharmacology/palbociclib/)
- [**Ribociclib** A 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)](https://durgical.com/en/pharmacology/ribociclib/)
- [**Abemaciclib** A 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)](https://durgical.com/en/pharmacology/abemaciclib/)

## 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.

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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](https://atcddd.fhi.no/atc_ddd_index/?code=L01EF) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [Palbociclib - NCI](https://www.cancer.gov/about-cancer/treatment/drugs/palbociclib) (National Cancer Institute, 2024).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/cdk4-6-inhibitors/