ArticleCell reports2016
Metabolic Reprogramming of Pancreatic Cancer Mediated by CDK4/6 Inhibition Elicits Unique Vulnerabilities.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 130 papers.
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
130 citing papers in PubMed, 196 citations in OpenAlex.
- Trial
- Rewiring the Molecular Interplay of CDK4/6 Inhibitors in Lung Cancer: From Cell Cycle Control to Immune Microenvironment Remodeling.International journal of molecular sciences · 2026Review
- Targeting PFKFB3 to enhance CDK4/6 inhibitor response in ER+ breast cancer.Breast cancer research : BCR · 2026Article
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas withBiomolecules & therapeutics · 2026Article
- Targeting PFKFB3 to enhance CDK4/6 inhibitor response in ER+ breast cancer.Research square · 2026Article
- MiR-181a-5p/CDK6 axis attenuates cell proliferation, migration and glycolytic reprogramming in oral squamous cell carcinoma.Cancer cell international · 2026Article
- The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity.Cancers · 2025Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- The landscape of cyclin-dependent kinase 4/6 inhibitors in solid malignancies: emphasis on immunotherapy combinatorial strategies.Medical oncology (Northwood, London, England) · 2025Review
- Apoptotic vesicles of mesenchymal stem cells promote M2 polarization and alleviate early-onset preeclampsia via miR-191-5p.Stem cell research & therapy · 2025Article
- Review
- CDK6 kinase inhibition unmasks metabolic dependencies in BCR::ABL1+ leukemia.Cell death & disease · 2025Article
- Article
- V-ATPase in glioma stem cells: a novel metabolic vulnerability.Journal of experimental & clinical cancer research : CR · 2025Article
- CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.Nature communications · 2025Article
- Safety assessment of cyclin-dependent kinase 4/6 inhibitors and comparison of time to adverse events.PloS one · 2025Article
- Inhibition of glutaminase elicits senolysis in therapy-induced senescent melanoma cells.Cell death & disease · 2024Article
- Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway.Translational oncology · 2024Article
- CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response.Cell death discovery · 2024Article
70 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Due to loss of p16ink4a in pancreatic ductal adenocarcinoma (PDA), pharmacological suppression of CDK4/6 could represent a potent target for treatment. In PDA models, CDK4/6 inhibition had a variable effect on cell cycle but yielded accumulation of ATP and mitochondria. Pharmacological CDK4/6 inhibitors induce cyclin D1 protein levels; however, RB activation was required and sufficient for mitochondrial accumulation. CDK4/6 inhibition stimulated glycolytic and oxidative metabolism and was associated with an increase in mTORC1 activity. MTOR and MEK inhibitors potently cooperate with CDK4/6 inhibition in eliciting cell-cycle exit. However, MTOR inhibition fully suppressed metabolism and yielded apoptosis and suppression of tumor growth in xenograft models. The metabolic state mediated by CDK4/6 inhibition increases mitochondrial number and reactive oxygen species (ROS). Concordantly, the suppression of ROS scavenging or BCL2 antagonists cooperated with CDK4/6 inhibition. Together, these data define the impact of therapeutics on PDA metabolism and provide strategies for converting cytostatic response to tumor cell killing.
Indexed as
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.