ArticleThe EMBO journal2022
CDK4/6 inhibitors induce replication stress to cause long-term cell cycle withdrawal.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Efficacy and safety of first-line CDK4/6 inhibitors plus AI therapy for patients with HR +/HER2- advanced breast cancer: a network meta-analysis.BMC cancer · 2025Pooled it
- Loss of Erbin in tubular epithelial cells sensitizes mice to acute kidney injury and aggravates renal fibrosis.The EMBO journal · 2026Article
- BUB1 and CDK4/6 Dual Inhibition Increases Radiation Sensitivity in Glioblastoma, Lung Cancer, and Triple-Negative Breast Cancer.Biomedicines · 2026Article
- Spatially defined microenvironmental niches are associated with clinical outcome and tumor ecosystem diversity in head and neck cancer.Med (New York, N.Y.) · 2026Article
- Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination.Nucleic acids research · 2026Article
- Molecular modulators of cyclin-dependent kinase 4/6 inhibitor response in experimental glioma identified through genome-wide CRISPR-Cas9 screening.Neuro-oncology · 2026Article
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- Impact of Iron Speciation on the Cytotoxicity and Gene Expression Profile of BiofortifiedMolecules (Basel, Switzerland) · 2026Article
- Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells.Cell death & disease · 2026Article
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Cell size modulates ferroptosis susceptibility.eLife · 2026Article
- Article
- Oncofertility in the Age of HER2 Blockade, Immunotherapy, PARP inhibitors, CDK4/6 inhibitors and Endocrine Treatment: Unanswered Questions in Breast Cancer.Current treatment options in oncology · 2026Review
- CDK4/6 inhibition uncovers subtype-specific vulnerabilities and immune-related responses in esophageal squamous cell carcinoma.Cell death & disease · 2026Article
- Chromosomal instability promotes cell migration and invasion via EFEMP1 secretion into extracellular vesicles.The EMBO journal · 2026Article
- Review
- Pseudo-senescence induced by palbociclib does not sensitise pleural mesothelioma cells to combinations with senolytics.Cell death & disease · 2026Article
- Cell confinement initiates a delayed but heritable loss of chromosomes.Cell reports · 2026Article
- Cell size modulates ferroptosis susceptibility.bioRxiv : the preprint server for biology · 2026Article
- HES1 oscillations are required for cell cycle reentry in oestrogen receptor-positive breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
CDK4/6 inhibitors arrest the cell cycle in G1-phase. They are approved to treat breast cancer and are also undergoing clinical trials against a range of other tumour types. To facilitate these efforts, it is important to understand why a cytostatic arrest in G1 causes long-lasting effects on tumour growth. Here, we demonstrate that a prolonged G1 arrest following CDK4/6 inhibition downregulates replisome components and impairs origin licencing. Upon release from that arrest, many cells fail to complete DNA replication and exit the cell cycle in a p53-dependent manner. If cells fail to withdraw from the cell cycle following DNA replication problems, they enter mitosis and missegregate chromosomes causing excessive DNA damage, which further limits their proliferative potential. These effects are observed in a range of tumour types, including breast cancer, implying that genotoxic stress is a common outcome of CDK4/6 inhibition. This unanticipated ability of CDK4/6 inhibitors to induce DNA damage now provides a rationale to better predict responsive tumour types and effective combination therapies, as demonstrated by the fact that CDK4/6 inhibition induces sensitivity to chemotherapeutics that also cause replication stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.