ArticleCancers2023
Stromal Senescence following Treatment with the CDK4/6 Inhibitor Palbociclib Alters the Lung Metastatic Niche and Increases Metastasis of Drug-Resistant Mammary Cancer Cells.
Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- Translational Geroscience Strategies for Delaying Multimorbidity.ACS pharmacology & translational science · 2026Review
- Senescence-associated gene signatures predict survival in lung cancer: a multi-cohort analysis.GeroScience · 2026Article
- Senescent cell clearance suppresses post-radiotherapy glioblastoma recurrence via the IL-6/JAK2/STAT3 pathway.Molecular and cellular biochemistry · 2026Article
- Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- Estrogen Receptors as Key Factors in Carcinogenesis.Biomedicines · 2025Review
- Spatial Omics Profiling of Treatment-Naïve Lung Adenocarcinoma with Brain Metastasis as the Initial Presentation.Cancers · 2025Article
- Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.Nature aging · 2025Article
- Endothelium as a Source of Cardiovascular Toxicity From Antitumor Kinase Inhibitors.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?International journal of molecular sciences · 2023Review
- Ratios of monocytes and neutrophils to lymphocytes in the blood predict benefit of CDK4/6 inhibitor treatment in metastatic breast cancer.Scientific reports · 2023Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCDK4/6 inhibitors (CDKi) have improved disease control in hormone-receptor-positive, HER2-negative metastatic breast cancer, but most patients develop progressive disease.
methodsWe asked whether host stromal senescence after CDK4/6 inhibition affects metastatic seeding and growth of CDKi-resistant mammary cancer cells by using the p16-INK-ATTAC mouse model of inducible senolysis.
resultsPalbociclib pretreatment of naïve mice increased lung seeding of CDKi-resistant syngeneic mammary cancer cells, and this effect was reversed by depletion of host senescent cells. RNA sequencing analyses of lungs from non-tumor-bearing p16-INK-ATTAC mice identified that palbociclib downregulates immune-related gene sets and gene expression related to leukocyte migration. Concomitant senolysis reversed a portion of these effects, including pathway-level enrichment of TGF-β- and senescence-related signaling. CIBERSORTx analysis revealed that palbociclib alters intra-lung macrophage/monocyte populations. Notably, lung metastases from palbociclib-pretreated mice revealed senescent endothelial cells. Palbociclib-treated endothelial cells exhibit hallmark senescent features in vitro, upregulate genes involved with the senescence-associated secretory phenotype, leukocyte migration, and TGF-β-mediated paracrine senescence and induce tumor cell migration and monocyte trans-endothelial invasion in co-culture.
conclusionsThese studies shed light on how stromal senescence induced by palbociclib affects lung metastasis, and they describe palbociclib-induced gene expression changes in the normal lung and endothelial cell models that correlate with changes in the tumor microenvironment in the lung metastatic niche.
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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.