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Updated: Feb 1, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Cyclin-dependent kinase 4/6 inhibitors: what have we learnt across studies, therapy situations and substances
Malgorzata Banys-Paluchowski1, Natalia Krawczyk2, Peter Paluchowski3
1Department of Gynecology and Obstetrics, Asklepios Klinik Barmbek, Hamburg.
Purpose Of Review:
Cyclin-dependent kinases (CDK) are key regulatory enzymes that control cell cycle and cell division. In the recent years, new therapeutic options selectively targeting CDK 4 and 6 have shown promising clinical activity in several solid tumors. Since 2015, three CDK 4/6 inhibitors have been approved for treatment of hormone receptor-positive HER2-negative metastatic breast cancer: palbociclib, ribociclib and abemaciclib. These drugs share a common mechanism of action and have been evaluated in studies with a similar design. The following review gives a clinical overview of the CDK 4/6 inhibitors in breast cancer therapy and highlight current study data with regard to their antitumor efficacy and toxicities.
Recent Findings:
In clinical trials in the first-line and later-line setting, palbociclib, ribociclib and abemaciclib in combination with endocrine therapy significantly prolonged progression-free survival. The most common adverse events during treatment with CDK 4/6 inhibitors are neutropenia, fatigue and gastrointestinal symptoms.
Summary:
CDK 4/6 inhibitors represent a valuable treatment option for patients with metastatic hormone receptor-positive HER2-negative breast cancer. Although the clinical efficacy of the three agents seems similar, their toxicity profiles differ. Therefore, the choice of a CKD 4/6 inhibitor depends on patient's characteristics and individual preferences.
Video Abstract:
In the video, the author describes the content of the review and present the main topics discussed in the article (http://links.lww.com/COOG/A44).
Insights
New CDK 4/6 inhibitors, including palbociclib, ribociclib, and abemaciclib, offer effective treatment for metastatic breast cancer. While improving progression-free survival, careful consideration of individual patient profiles is essential due to differing toxicity.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Cyclin-dependent kinases (CDKs) regulate cell division.
- CDK 4/6 inhibitors have emerged as a significant therapeutic advance.
- Approved CDK 4/6 inhibitors include palbociclib, ribociclib, and abemaciclib.
Purpose of the Study:
- To provide a clinical overview of CDK 4/6 inhibitors in breast cancer.
- To highlight current data on antitumor efficacy and toxicities.
- To discuss the role of these agents in metastatic hormone receptor-positive HER2-negative breast cancer.
Main Methods:
- Review of clinical trial data for CDK 4/6 inhibitors.
- Analysis of progression-free survival data.
- Evaluation of adverse event profiles.
Main Results:
- CDK 4/6 inhibitors significantly prolonged progression-free survival in combination with endocrine therapy.
- Common adverse events include neutropenia, fatigue, and gastrointestinal issues.
- Clinical efficacy appears similar across agents, but toxicity profiles vary.
Conclusions:
- CDK 4/6 inhibitors are a valuable treatment for metastatic HR+/HER2- breast cancer.
- Individual patient characteristics and preferences should guide treatment selection.
- Understanding differing toxicity profiles is crucial for optimal patient management.
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