ArticleBritish journal of cancer2010
Pre-clinical evaluation of cyclin-dependent kinase 2 and 1 inhibition in anti-estrogen-sensitive and resistant breast cancer cells.
Article in British journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 66 citations in OpenAlex.
- Cyclin Dependent Kinase 2 (CDK2) Inhibitors in Oncology Clinical Trials: A Review.Journal of immunotherapy and precision oncology · 2025Review
- Inhibition of Dormant Lung Cancer Cell Reactivation byDrug design, development and therapy · 2025Article
- Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers.Molecular cancer research : MCR · 2023Article
- Aberrant APOBEC3B Expression in Breast Cancer Is Linked to Proliferation and Cell Cycle Phase.Cells · 2023Article
- Applications and mechanisms of the cyclin-dependent kinase 4/6 inhibitor, PD-0332991, in solid tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Identification of 3-(piperazinylmethyl)benzofuran derivatives as novel type II CDK2 inhibitors: design, synthesis, biological evaluation, andJournal of enzyme inhibition and medicinal chemistry · 2022Article
- Article
- Collateral-resistance to estrogen and HER-activated growth is associated with modified AKT, ERα, and cell-cycle signaling in a breast cancer model.Exploration of targeted anti-tumor therapy · 2022Article
- Crosstalk between the CBM complex/NF-κB and MAPK/P27 signaling pathways of regulatory T cells contributes to the tumor microenvironment.Frontiers in cell and developmental biology · 2022Review
- Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, andJournal of enzyme inhibition and medicinal chemistry · 2021Article
- Targeting cell-cycle machinery in cancer.Cancer cell · 2021Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
- Genome-wide analysis of therapeutic response uncovers molecular pathways governing tamoxifen resistance in ER+ breast cancer.EBioMedicine · 2020Article
- How Different Are the Molecular Mechanisms of Nodal and Distant Metastasis in Luminal A Breast Cancer?Cancers · 2020Article
- Protein Kinase Targets in Breast Cancer.International journal of molecular sciences · 2017Review
- FOXA1 expression affects the proliferation activity of luminal breast cancer stem cell populations.Cancer science · 2016Article
- Differential Regulation of Progesterone Receptor-Mediated Transcription by CDK2 and DNA-PK.Molecular endocrinology (Baltimore, Md.) · 2016Article
- The Role of MicroRNAs as Predictors of Response to Tamoxifen Treatment in Breast Cancer Patients.International journal of molecular sciences · 2015Review
- Insights on Structural Characteristics and Ligand Binding Mechanisms of CDK2.International journal of molecular sciences · 2015Review
- CDK2-AP1 inhibits growth of breast cancer cells by regulating cell cycle and increasing docetaxel sensitivity in vivo and in vitro.Cancer cell international · 2014Article
Corrections and comments
- Expression of concern
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCellular proliferation, driven by cyclin-dependent kinases (CDKs) and their cyclin partners, is deregulated in cancer. Anti-estrogens, such as tamoxifen, antagonise estrogen-induced ERalpha transactivation of cyclin D1, resulting in reduced CDK4/6 activity, p27(Kip1)-mediated inhibition of CDK2 and growth arrest. We hypothesised that direct inhibition of CDK2 and CDK1 may overcome the major clinical problem of anti-estrogen resistance.
methodsThe cellular effects of CDK2/1 siRNA knockdown and purine-based CDK2/1 inhibitors, NU2058 and NU6102, were measured in anti-estrogen-sensitive and resistant breast cancer cell lines.
resultsCDK2 knockdown caused G1 accumulation, whereas CDK1 depletion caused G2/M slowing, and dual CDK1/2 depletion resulted in further G2/M accumulation and cell death in both anti-estrogen-sensitive and resistant cells, confirming CDK2 and CDK1 as targets for breast cancer therapy. In contrast to tamoxifen, which only affected hormone-sensitive cells, NU2058 and NU6102 reduced CDK2-mediated phosphorylation of pRb, E2F transcriptional activity and proliferation, ultimately resulting in cell death, in both anti-estrogen-sensitive and resistant cells. Both drugs caused G2/M arrest, reflective of combined CDK2/1 knockdown, with a variable degree of G1 accumulation.
conclusionThese studies confirm the therapeutic potential of CDK2 and CDK1 inhibitors for cancer therapy, and support their use as an alternative treatment for endocrine-resistant breast cancer.
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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.