ArticleJCI insight2022
RB expression confers sensitivity to CDK4/6 inhibitor-mediated radiosensitization across breast cancer subtypes.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- CDK4/6 inhibitors as conditional immune-priming agents in breast cancer: therapeutic windows, sequencing strategies, and rational combinations with immunotherapy, radiotherapy, and antibody-drug conjugates.Frontiers in immunology · 2026Pooled it
- Models of Early Resistance to CDK4/6 Inhibitors Unveil Potential Therapeutic Treatment Sequencing.International journal of molecular sciences · 2025Trial
- Triple-Negative Transformation in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: Tissue Versus Liquid Biopsy in Two Cases.JCO precision oncology · 2026Article
- Molecular signatures of triple-negative breast cancer cells acquiring palbociclib resistance via continuous exposure.Oncology letters · 2026Article
- BUB1 and CDK4/6 Dual Inhibition Increases Radiation Sensitivity in Glioblastoma, Lung Cancer, and Triple-Negative Breast Cancer.Biomedicines · 2026Article
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Oxidative stress and antioxidants in breast cancer: a double-edged sword.Frontiers in oncology · 2026Review
- Enhancing radiosensitivity of boron neutron capture therapy for liver cancer with homologous recombination repair inhibitor.Japanese journal of radiology · 2026Article
- Article
- Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.Oncogene · 2025Article
- CDK4/6 inhibitors synergize with radiotherapy to prime the tumor microenvironment and enhance the antitumor effect of anti-PD-L1 immunotherapy in triple-negative breast cancer.Journal of biomedical science · 2025Article
- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
- Palliative Radiotherapy in Metastatic Breast Cancer Patients on CDK4/6 Inhibitors: Safety Analysis.Cancers · 2025Article
- CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response.Cell death discovery · 2024Article
- Cellular senescence in the response of HRJournal of translational medicine · 2023Article
- Cancer-testis antigen CEP55 serves as a prognostic biomarker and is correlated with immune infiltration and immunotherapy efficacy in pan-cancer.Frontiers in molecular biosciences · 2023Article
- A new perspective on the proper timing of radiotherapy during CDK4/6 inhibitor therapy in patients with "bone-only" metastatic breast cancer.Pathology oncology research : POR · 2023Review
- Down-regulation ofInternational journal of molecular epidemiology and genetics · 2023Article
- Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer.British journal of cancer · 2022Article
- Melatonin Modulation of Radiation-Induced Molecular Changes in MCF-7 Human Breast Cancer Cells.Biomedicines · 2022Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Standard radiation therapy (RT) does not reliably provide locoregional control for women with multinode-positive breast cancer and triple-negative breast cancer (TNBC). We hypothesized that CDK4/6 inhibition (CDK4/6i) would increase the radiosensitivity not only of estrogen receptor-positive (ER+) cells, but also of TNBC that expresses retinoblastoma (RB) protein. We found that CDK4/6i radiosensitized RB WT TNBC (n = 4, radiation enhancement ratio [rER]: 1.49-2.22) but failed to radiosensitize RB-null TNBC (n = 3, rER: 0.84-1.00). RB expression predicted response to CDK4/6i + RT (R2 = 0.84), and radiosensitization was lost in ER+/TNBC cells (rER: 0.88-1.13) after RB1 knockdown in isogenic and nonisogenic models. CDK4/6i suppressed homologous recombination (HR) in RB WT cells but not in RB-null cells or isogenic models of RB1 loss; HR competency was rescued with RB reexpression. Radiosensitization was independent of nonhomologous end joining and the known effects of CDK4/6i on cell cycle arrest. Mechanistically, RB and RAD51 interact in vitro to promote HR repair. CDK4/6i produced RB-dependent radiosensitization in TNBC xenografts but not in isogenic RB1-null xenografts. Our data provide the preclinical rationale for a clinical trial expanding the use of CDK4/6i + RT to difficult-to-control RB-intact breast cancers (including TNBC) and nominate RB status as a predictive biomarker of therapeutic efficacy.
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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.