ArticleOncotarget2014
CDK4/6 inhibitors have potent activity in combination with pathway selective therapeutic agents in models of pancreatic cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 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
129 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- Germline Variants and Risk for Pancreatic Cancer: A Systematic Review and Emerging Concepts.Pancreas · 2018Pooled it
- Trial
- Genomic and Immune Landscape of Pancreatic Ductal Adenocarcinoma Associated with Germline Pathogenic Variants in ATM.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Review
- Chemosensitization and Molecular Docking Assessment of Dio-NPs on Resistant Breast Cancer Cells to Tamoxifen.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Resistance mechanisms and therapeutic strategies of CDK4 and CDK6 kinase targeting in cancer.Nature cancer · 2025Review
- CDK4/6 and BET inhibitors synergistically suppress pancreatic tumor growth and epithelial-to-mesenchymal transition by regulating the GSK3β-mediated Wnt/β-catenin pathway.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.Molecular oncology · 2024Article
- Review
- CCNI2 promotes pancreatic cancer through PI3K/AKT signaling pathway.Biomolecules & biomedicine · 2024Article
- Pharmacological modulation of RB1 activity mitigates resistance to neoadjuvant chemotherapy in locally advanced rectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Recent advances in drug delivery and targeting for the treatment of pancreatic cancer.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Inhibition of the RAF/MEK/ERK Signaling Cascade in Pancreatic Cancer: Recent Advances and Future Perspectives.International journal of molecular sciences · 2024Review
- Article
- Therapy for Hormone Receptor-Positive, Human Epidermal Growth Receptor 2-Negative Metastatic Breast Cancer Following Treatment Progression via CDK4/6 Inhibitors: A Literature Review.Breast cancer (Dove Medical Press) · 2024Review
- Article
- Combined Inhibition ofInternational journal of molecular sciences · 2023Article
- CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.Cell cycle (Georgetown, Tex.) · 2023Article
- A narrative review about CDK4/6 inhibitors in the setting of drug resistance: updates on biomarkers and therapeutic strategies in breast cancer.Translational cancer research · 2023Review
- Predicting anti-cancer drug combination responses with a temporal cell state network model.PLoS computational biology · 2023Article
69 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
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, in part, due to the therapy-recalcitrant nature of the disease. Loss of the CDK4/6 inhibitor CDKN2A is a signature genetic event in PDA. Therefore, PDA may be amenable to treatment with pharmaceutical CDK4/6 inhibitors. Surprisingly, response to CDK4/6 inhibition was highly variable in PDA models, and associated with differential suppression of gene expression. Mitotic genes were repressed and FOXM1 was uniformly attenuated; however, genes involved in DNA replication were uniquely suppressed in sensitive models. Aberrant induction of Cyclin E1 was associated with resistance, and knockdown demonstrated synergistic suppression of the cell cycle with CDK4/6 inhibition. Combination therapies are likely required for the effective treatment of disease, and drug screening demonstrated additive/antagonistic interactions with CDK4/6 inhibitors. Agents dependent on mitotic progression (taxanes/PLK1 inhibitors) were antagonized by CDK4/6 inhibition, while the response to 5-FU and gemcitabine exhibited drug specific interactions. PI3K/MTOR and MEK inhibitors potently cooperated with CDK4/6 inhibition. These agents were synergistic with CDK4/6 inhibition, blocked the aberrant upregulation of Cyclin E1, and yielded potent inhibition of tumor cell growth. Together, these data identify novel mechanisms of resistance to CDK4/6 inhibitions and provide a roadmap for combination therapies in the treatment of PDA.
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.