ArticleNature communications2017
CDK4/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin E negative cancers.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
189 citing papers in PubMed, 1 synthesis or guideline pooled it, 274 citations in OpenAlex.
- Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer.JCO precision oncology · 2022Pooled it
- Cyclin E1 Expression and Palbociclib Efficacy in Previously Treated Hormone Receptor-Positive Metastatic Breast Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Decline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cells.Nature aging · 2026Article
- CDK8/19 inhibition prevents adaptive resistance to CDK4/6 inhibitors in vitro and in vivo.Cell reports. Medicine · 2026Article
- IL-8 blockade enhances anti-PD-1 therapeutic activity in renal cell carcinoma in a next-generation patient-derived xenograft model.iScience · 2026Article
- From Inflammatory RNAs to Therapeutic Silencing: Deciphering the RNA-Inflammation Axis in Cancer and Neurodegeneration.Biology · 2026Review
- Real-world study of treatment patterns and outcomes in patients with HR+ breast cancer after progression on CDK4/6 inhibitor therapy.Lancet regional health. Americas · 2026Article
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Review
- Fate Bifurcation of Cellular Senescence: Dynamic Regulation from Tumor Suppression to Recurrence Risk.Cells · 2026Review
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Article
- Article
- mTOR-driven autophagy suppression defines metabolic vulnerability in CDK4/6 inhibitor-resistant HRCell death & disease · 2026Article
- CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.Nature communications · 2026Article
- CDK4/6 inhibition overcomes venetoclax resistance mechanisms with enhanced combination activity in acute myeloid leukemia.Cell reports. Medicine · 2026Article
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- BRSK2 plays a role in autophagy and cancer cell growth and survival under nutrient deprivation stress via the PIK3C3 pathway.Scientific reports · 2025Article
- Advances in Cutaneous Melanoma Therapy: The Emerging Role of CDK4/6 Inhibitors.Pharmacological research · 2025Review
129 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Deregulation of the cell cycle machinery is a hallmark of cancer. While CDK4/6 inhibitors are FDA approved (palbociclib) for treating advanced estrogen receptor-positive breast cancer, two major clinical challenges remain: (i) adverse events leading to therapy discontinuation and (ii) lack of reliable biomarkers. Here we report that breast cancer cells activate autophagy in response to palbociclib, and that the combination of autophagy and CDK4/6 inhibitors induces irreversible growth inhibition and senescence in vitro, and diminishes growth of cell line and patient-derived xenograft tumours in vivo. Furthermore, intact G1/S transition (Rb-positive and low-molecular-weight isoform of cyclin E (cytoplasmic)-negative) is a reliable prognostic biomarker in ER positive breast cancer patients, and predictive of preclinical sensitivity to this drug combination. Inhibition of CDK4/6 and autophagy is also synergistic in other solid cancers with an intact G1/S checkpoint, providing a novel and promising biomarker-driven combination therapeutic strategy to treat breast and other solid tumours.
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Identifiers
What OpenQuestion holds
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.