ArticleOncogene2016
Molecular basis underlying resistance to Mps1/TTK inhibitors.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 67 citations in OpenAlex.
- Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting.International journal of molecular sciences · 2026Review
- Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies.Pharmaceutics · 2026Review
- Polar chromosomes are rescued from missegregation by spindle elongation-driven microtubule pivoting.Nature communications · 2026Article
- Chemical Genetics with SP600125 Reveals That Mps1 Protein Kinase Works as a Regulatory Element in Post-embryonic Development of theACS omega · 2025Article
- Targeting monopolar spindle kinase I (Mps1 or TTK) induces radiosensitization in syngeneic models of triple negative breast cancer (TNBC) and potentiates type I interferon (T1IFN) signaling.Neoplasia (New York, N.Y.) · 2025Article
- Dual Targeting of Pim and PI3 Kinases in Mature T-Cell Lymphoma.European journal of haematology · 2025Article
- Proximity-based activation of AURORA A by MPS1 potentiates error correction.Current biology : CB · 2025Article
- Transcriptomic analysis revealed potential regulatory biomarkers and repurposable drugs for breast cancer treatment.Cancer reports (Hoboken, N.J.) · 2024Article
- Upregulation of TTK expression is associated with poor prognosis and immune infiltration in endometrial cancer patients.Cancer cell international · 2024Article
- Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.Genes & development · 2023Article
- Computational Biology Dynamics of Mps1 Kinase Molecular Interactions with Isoflavones Reveals a Chemical Scaffold with Potential to Develop New Therapeutics for the Treatment of Cancer.International journal of molecular sciences · 2022Article
- Article
- Phosphotyrosine picked threonine kinase stimulates proliferation of human osteosarcoma cellsArchives of medical science : AMS · 2022Article
- TTK inhibition increases cisplatin sensitivity in high-grade serous ovarian carcinoma through the mTOR/autophagy pathway.Cell death & disease · 2021Article
- Tank Binding Kinase 1 modulates spindle assembly checkpoint components to regulate mitosis in breast and lung cancer cells.Biochimica et biophysica acta. Molecular cell research · 2021Article
- LAHMA: structure analysis through local annotation of homology-matched amino acids.Acta crystallographica. Section D, Structural biology · 2021Article
- Interrogation of kinase genetic interactions provides a global view of PAK1-mediated signal transduction pathways.The Journal of biological chemistry · 2020Article
- [Spindle assembly checkpoint complex-related genes TTK and MAD2L1 are over-expressed in lung adenocarcinoma: a big data and bioinformatics analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Broad-spectrum antitumor properties of Withaferin A: a proteomic perspective.RSC medicinal chemistry · 2020Review
- Ectopic Activation of the Spindle Assembly Checkpoint Signaling Cascade Reveals Its Biochemical Design.Current biology : CB · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mps1/TTK is a dual-specificity kinase, with an essential role in mitotic checkpoint signaling, which has emerged as a potential target in cancer therapy. Several Mps1/TTK small-molecule inhibitors have been described that exhibit promising activity in cell culture and xenograft models. Here, we investigated whether cancer cells can develop resistance to these drugs. To this end, we treated various cancer cell lines with sublethal concentrations of a potent Mps1/TTK inhibitor in order to isolate inhibitor-resistant monoclonal cell lines. We identified four point mutations in the catalytic domain of Mps1/TTK that gave rise to inhibitor resistance but retained wild-type catalytic activity. Interestingly, cross-resistance of the identified mutations to other Mps1/TTK inhibitors is limited. Our studies predict that Mps1/TTK inhibitor-resistant tumor cells can arise through the acquisition of mutations in the adenosine triphosphate-binding pocket of the kinase that prevent stable binding of the inhibitors. In addition, our results suggest that combinations of inhibitors could be used to prevent acquisition of drug resistance. Interestingly, cross-resistance seems nonspecific for inhibitor scaffolds, a notion that can be exploited in future drug design to evict possible resistance mutations during clinical treatment.
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.