ArticleOncotarget2016
MLN-8237: A dual inhibitor of aurora A and B in soft tissue sarcomas.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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
21 citing papers in PubMed, 34 citations in OpenAlex.
- Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2016Trial
- Article
- Selective Aurora A-TPX2 Interaction Inhibitors HaveJournal of medicinal chemistry · 2024Article
- Selective Xi reactivation and alternative methods to restore MECP2 function in Rett syndrome.Trends in genetics : TIG · 2022Review
- Review
- Beyond targeting amplified MDM2 and CDK4 in well differentiated and dedifferentiated liposarcomas: From promise and clinical applications towards identification of progression drivers.Frontiers in oncology · 2022Review
- Article
- Recent Advancement in Atypical Lipomatous Tumor Research.International journal of molecular sciences · 2021Review
- Article
- RACK1 affects the progress of G2/M by regulating Aurora-A.Cell cycle (Georgetown, Tex.) · 2019Article
- Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics.Cell death & disease · 2019Article
- Precision Oncology in Sarcomas: Divide and Conquer.JCO precision oncology · 2019Review
- Microtubule polyglutamylation and acetylation drive microtubule dynamics critical for platelet formation.BMC biology · 2018Article
- Clinical and Molecular Spectrum of Liposarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Review
- Preclinical evaluation of the Aurora kinase inhibitors AMG 900, AZD1152-HQPA, and MK-5108 on SW-872 and 93T449 human liposarcoma cells.In vitro cellular & developmental biology. Animal · 2018Article
- Heterogeneity in sarcoma cell lines reveals enhanced motility of tetraploid versus diploid cells.Oncotarget · 2017Article
- Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma.Oncotarget · 2017Article
- Recent translational research into targeted therapy for liposarcoma.Stem cell investigation · 2017Review
- Phosphorylation of MAP65-1 by Arabidopsis Aurora Kinases Is Required for Efficient Cell Cycle Progression.Plant physiology · 2017Article
- A high-throughput small molecule screen identifies synergism between DNA methylation and Aurora kinase pathways for X reactivation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Aurora kinases have become an attractive target in cancer therapy due to their deregulated expression in human tumors. Liposarcoma, a type of soft tissue sarcoma in adults, account for approximately 20% of all adult soft tissue sarcomas. There are no effective chemotherapies for majority of these tumors. Efforts made to define the molecular basis of liposarcomas lead to the finding that besides the amplifications of CDK4 and MDM2, Aurora Kinase A, also was shown to be overexpressed. Based on these as well as mathematic modeling, we have carried out a successful preclinical study using CDK4 and IGF1R inhibitors in liposarcoma. MLN8237 has been shown to be a potent and selective inhibitor of Aurora A. MLN-8237, as per our results, induces a differential inhibition of Aurora A and B in a dose dependent manner. At a low nanomolar dose, cellular effects such as induction of phospho-Histone H3 (Ser10) mimicked as that of the inhibition of Aurora kinase A followed by apoptosis. However, micromolar dose of MLN-8237 induced polyploidy, a hallmark effect of Aurora B inhibition. The dose dependent selectivity of inhibition was further confirmed by using siRNA specific inhibition of Aurora A and B. This was further tested by time lapse microscopy of GFP-H2B labelled cells treated with MLN-8237. LS141 xenograft model at a dose of 30 mg/kg also showed efficient growth suppression by selective inhibition of Aurora Kinase A. Based on our data, a dose that can target only Aurora A will be more beneficial in tumor suppression.
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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.