ArticleJournal of the National Cancer Institute2017
Next-Generation CDK2/9 Inhibitors and Anaphase Catastrophe in Lung Cancer.
Article in Journal of the National Cancer Institute, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting KIFC1 to disrupt centrosome clustering and trigger anaphase catastrophe in small-cell lung cancer.JCI insight · 2026Article
- CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.Nature communications · 2026Article
- Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Dual targeting of conserved cell cycle and transcription programs in advanced colorectal cancer by fadraciclib.Evolution, medicine, and public health · 2025Article
- P129, a pyrazole ring-containing isolongifolanone-derivate: synthesis and investigation of anti-glioma action mechanism.Discover oncology · 2024Article
- CDK2 inhibition disorders centrosome stoichiometry and alters cellular outcomes in aneuploid cancer cells.Cancer biology & therapy · 2023Article
- New spiro-indeno[1,2-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Cigarette smoke condensate induces centrosome clustering in normal lung epithelial cells.Cancer medicine · 2023Article
- A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle.Molecules (Basel, Switzerland) · 2023Review
- Loss of ubiquitin-specific peptidase 18 destabilizes 14-3-3ζ protein and represses lung cancer metastasis.Cancer biology & therapy · 2022Article
- A review on the role of cyclin dependent kinases in cancers.Cancer cell international · 2022Review
- Integrating Network Pharmacology, Molecular Docking, and Experimental Validation to Investigate the Mechanism of (-)-Guaiol Against Lung Adenocarcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2022Article
- CDK9 inhibitors in cancer research.RSC medicinal chemistry · 2022Review
- LINC00265 Promotes Metastasis and Progression of Hepatocellular Carcinoma by Interacting with E2F1 at The Promoter ofCell journal · 2022Article
- The Ubiquitin-Specific Peptidase USP18 Promotes Lipolysis, Fatty Acid Oxidation, and Lung Cancer Growth.Molecular cancer research : MCR · 2021Article
- A Novel CDK2/9 Inhibitor CYC065 Causes Anaphase Catastrophe and Represses Proliferation, Tumorigenesis, and Metastasis in Aneuploid Cancers.Molecular cancer therapeutics · 2021Article
- NTF3 Correlates With Prognosis and Immune Infiltration in Hepatocellular Carcinoma.Frontiers in medicine · 2021Article
- A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer.Molecular cancer therapeutics · 2020Article
- Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.The Journal of clinical investigation · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Background: The first generation CDK2/7/9 inhibitor seliciclib (CYC202) causes multipolar anaphase and apoptosis in lung cancer cells with supernumerary centrosomes (known as anaphase catastrophe). We investigated a new and potent CDK2/9 inhibitor, CCT68127 (Cyclacel). Methods: CCT68127 was studied in lung cancer cells (three murine and five human) and control murine pulmonary epithelial and human immortalized bronchial epithelial cells. Robotic CCT68127 cell-based proliferation screens were used. Cells undergoing multipolar anaphase and inhibited centrosome clustering were scored. Reverse phase protein arrays (RPPAs) assessed CCT68127 effects on signaling pathways. The function of PEA15, a growth regulator highlighted by RPPAs, was analyzed. Syngeneic murine lung cancer xenografts (n = 4/group) determined CCT68127 effects on tumorigenicity and circulating tumor cell levels. All statistical tests were two-sided. Results: CCT68127 inhibited growth up to 88.5% (SD = 6.4%, P < .003) at 1 μM, induced apoptosis up to 42.6% (SD = 5.5%, P < .001) at 2 μM, and caused G1 or G2/M arrest in lung cancer cells with minimal effects on control cells (growth inhibition at 1 μM: 10.6%, SD = 3.6%, P = .32; apoptosis at 2 μM: 8.2%, SD = 1.0%, P = .22). A robotic screen found that lung cancer cells with KRAS mutation were particularly sensitive to CCT68127 ( P = .02 for IC 50 ). CCT68127 inhibited supernumerary centrosome clustering and caused anaphase catastrophe by 14.1% (SD = 3.6%, P < .009 at 1 μM). CCT68127 reduced PEA15 phosphorylation by 70% (SD = 3.0%, P = .003). The gain of PEA15 expression antagonized and its loss enhanced CCT68127-mediated growth inhibition. CCT68127 reduced lung cancer growth in vivo ( P < .001) and circulating tumor cells ( P = .004). Findings were confirmed with another CDK2/9 inhibitor, CYC065. Conclusions: Next-generation CDK2/9 inhibition elicits marked antineoplastic effects in lung cancer via anaphase catastrophe and reduced PEA15 phosphorylation.
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.