ArticleThe EMBO journal2022
Pharmacological CDK4/6 inhibition reveals a p53-dependent senescent state with restricted toxicity.
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 79 papers.
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Who cites it
79 citing papers in PubMed, 98 citations in OpenAlex.
- Targeting SUV39H2 exon skipping reverses resistance to CDK4/6 inhibitors via transcriptional activation of p21.Science advances · 2026Article
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- Loss of Erbin in tubular epithelial cells sensitizes mice to acute kidney injury and aggravates renal fibrosis.The EMBO journal · 2026Article
- CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation.Life science alliance · 2026Article
- Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.Nature aging · 2026Article
- Disruption of macrophage migration inhibitory factor signaling induces major tumor-associated macrophage phenotypes in human M2 macrophages.Molecular biomedicine · 2026Article
- Molecular Mechanisms and Molecular Subtype-Specific Responses to Paclitaxel in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- Small molecule activators of the mitochondrial protease ClpP induce senescence in triple-negative breast cancer cells and sensitize cells to the Bcl-2 inhibitor venetoclax.Cell death & disease · 2026Article
- HES1 inhibition overcomes CDK4/6 inhibitor resistance by targeting cancer stemness in lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells.Cell death & disease · 2026Article
- Article
- Review
- Pseudo-senescence induced by palbociclib does not sensitise pleural mesothelioma cells to combinations with senolytics.Cell death & disease · 2026Article
- A spatiotemporal atlas of senescence-associated secretory phenotype in fracture healing: stage-dependent mechanisms and therapeutic windows.Inflammation and regeneration · 2026Review
- Mitochondrial bioenergetics-SASP crosstalk determines senolytic efficacy in therapy-induced senescence.Cell death discovery · 2026Article
- Non-Canonical Senescence Phenotype in Resistance to CDK4/6 Inhibitors in ER-Positive Breast Cancer.Biomolecules · 2026Article
- Research progress on the spatiotemporal dynamics of therapy-induced senescence in remodeling the tumor microenvironment.Frontiers in immunology · 2026Review
- Stratified and Quantified Score Construction of Low-Grade Glioma Samples Based on TP53 Signaling Pathway.BioMed research international · 2026Article
- Fibroblast transformation in the tumor microenvironment of lung adenocarcinoma: heterogeneity, regulation, and therapeutic targeting.Frontiers in immunology · 2026Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular senescence is a state of stable growth arrest and a desired outcome of tumor suppressive interventions. Treatment with many anti-cancer drugs can cause premature senescence of non-malignant cells. These therapy-induced senescent cells can have pro-tumorigenic and pro-disease functions via activation of an inflammatory secretory phenotype (SASP). Inhibitors of cyclin-dependent kinases 4/6 (CDK4/6i) have recently proven to restrain tumor growth by activating a senescence-like program in cancer cells. However, the physiological consequence of exposing the whole organism to pharmacological CDK4/6i remains poorly characterized. Here, we show that exposure to CDK4/6i induces non-malignant cells to enter a premature state of senescence dependent on p53. We observe in mice and breast cancer patients that the CDK4/6i-induced senescent program activates only a partial SASP enriched in p53 targets but lacking pro-inflammatory and NF-κB-driven components. We find that CDK4/6i-induced senescent cells do not acquire pro-tumorigenic and detrimental properties but retain the ability to promote paracrine senescence and undergo clearance. Our results demonstrate that SASP composition is exquisitely stress-dependent and a predictor for the biological functions of different senescence subsets.
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