ArticleOncotarget2017
Stable aneuploid tumors cells are more sensitive to TTK inhibition than chromosomally unstable cell lines.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 37 citations in OpenAlex.
- Disconnect between in vitro and in vivo efficacy of the MPS1 inhibitor NTRC 0066-0 against glioblastoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Comparative profiling of osimertinib and fourth-generation EGFR inhibitors on EGFR-mutant proteins and cell lines.Frontiers in oncology · 2026Article
- Synthesis and Absolute Configuration of the Sesquiterpene Lactone EPD, a Natural Product with Broad Antitumor Cell Activity via a Unique Mechanism of Action.Journal of natural products · 2025Article
- Individualized Pooled CRISPR/Cas9 Screenings Identify CDK2 as a Druggable Vulnerability in a Canine Mammary Carcinoma Patient.Veterinary sciences · 2025Article
- Combined cellular and biochemical profiling of Bruton's tyrosine kinase inhibitor nemtabrutinib reveals potential application in MAPK-driven cancers.Frontiers in oncology · 2025Article
- Reduction of chromosomal instability and inflammation is a common aspect of adaptation to aneuploidy.EMBO reports · 2024Article
- Endogenous oncogenic KRAS expression increases cell proliferation and motility in near-diploid hTERT RPE-1 cells.The Journal of biological chemistry · 2024Article
- Comprehensively analyzing the genetic alterations, and identifying key genes in ovarian cancer.Oncology research · 2023Article
- CDK4/6 inhibitors induce replication stress to cause long-term cell cycle withdrawal.The EMBO journal · 2022Article
- Comparative kinase and cancer cell panel profiling of kinase inhibitors approved for clinical use from 2018 to 2020.Frontiers in oncology · 2022Article
- Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27.Open biology · 2021Article
- Pharmacological validation of TDO as a target for Parkinson's disease.The FEBS journal · 2021Article
- Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers.Oncogene · 2021Article
- Review
- TTK regulates proliferation and apoptosis of gastric cancer cells through the Akt-mTOR pathway.FEBS open bio · 2020Article
- Targeting Indoleamine 2,3-Dioxygenase in Cancer Models Using the Novel Small Molecule Inhibitor NTRC 3883-0.Frontiers in immunology · 2020Article
- Glutathione reductase (American journal of cancer research · 2019Article
- TTK promotes mesenchymal signaling via multiple mechanisms in triple negative breast cancer.Oncogenesis · 2018Article
- Insights into Resistance Mechanisms of Inhibitors to Mps1 C604Y Mutation via a Comprehensive Molecular Modeling Study.Molecules (Basel, Switzerland) · 2018Article
- The live cell DNA stain SiR-Hoechst induces DNA damage responses and impairs cell cycle progression.Scientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of the spindle assembly checkpoint kinase TTK causes chromosome mis-segregation and tumor cell death. However, high levels of TTK correlate with chromosomal instability (CIN), which can lead to aneuploidy. We show that treatment of tumor cells with the selective small molecule TTK inhibitor NTRC 0066-0 overrides the mitotic checkpoint, irrespective of cell line sensitivity. In stable aneuploid cells NTRC 0066-0 induced acute CIN, whereas in cells with high levels of pre-existing CIN there was only a small additional fraction of cells mis-segregating their chromosomes. In proliferation assays stable aneuploid cells were more sensitive than cell lines with pre-existing CIN. Tetraploids are thought to be an intermediate between diploid and unstable aneuploid cells. TTK inhibitors had the same potency on post-tetraploid and parental diploid cells, which is remarkable because the post-tetraploids are more resistant to mitotic drugs. Finally, we confirm that the reference compound reversine is a TTK inhibitor and like NTRC 0066-0, inhibits the proliferation of patient-derived colorectal cancer organoids. In contrast, treatment with TTK inhibitor did not reduce the viability of non-proliferating T cell acute lymphoblastic leukemia cells samples. Consequently, TTK inhibitor therapy is expected to spare non-dividing cells, and may be used to target stable aneuploid tumors.
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.