ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
A small-molecule inhibitor targeting the mitotic spindle checkpoint impairs the growth of uterine leiomyosarcoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 57 citations in OpenAlex.
- A phase 2 study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group study 0231D.Gynecologic oncology · 2017Trial
- Transcriptome profiling of uterine leiomyosarcomas identifies a leiomyoma-like expression pattern that indicates better survival.BJC reports · 2025Article
- Potential Markers to Differentiate Uterine Leiomyosarcomas from Leiomyomas.International journal of medical sciences · 2024Review
- Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach.Oncology reports · 2023Article
- The Expression of the Immunoproteasome Subunit PSMB9 Is Related to Distinct Molecular Subtypes of Uterine Leiomyosarcoma.Cancers · 2022Article
- FKBP51 Contributes to Uterine Leiomyoma Pathogenesis by Inducing Cell Proliferation and Extracellular Matrix Deposition.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Aberrant Activation of Cell-Cycle-Related Kinases and the Potential Therapeutic Impact of PLK1 or CHEK1 Inhibition in Uterine Leiomyosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma.International journal of molecular sciences · 2022Article
- Bioinformatics Analysis Identified Five Widely Expressed Genes Associated with Prognosis in Sarcoma.International journal of general medicine · 2022Article
- Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy.Molecular cancer · 2021Review
- The critical role of dysregulated Hh-FOXM1-TPX2 signaling in human hepatocellular carcinoma cell proliferation.Cell communication and signaling : CCS · 2020Article
- Insights into the non-mitotic functions of Aurora kinase A: more than just cell division.Cellular and molecular life sciences : CMLS · 2020Review
- Role of PLK1 signaling pathway genes in gastrointestinal stromal tumors.Oncology letters · 2018Article
- A review of soft-tissue sarcomas: translation of biological advances into treatment measures.Cancer management and research · 2018Review
- A Role for Progesterone-Regulated sFRP4 Expression in Uterine Leiomyomas.The Journal of clinical endocrinology and metabolism · 2017Article
- The Aurora kinase A inhibitor TC-A2317 disrupts mitotic progression and inhibits cancer cell proliferation.Oncotarget · 2016Article
- Increased Expression of Phosphorylated Polo-Like Kinase 1 and Histone in Bypass Vein Graft and Coronary Arteries following Angioplasty.PloS one · 2016Article
- Review
- Molecular subtypes of uterine leiomyosarcoma and correlation with clinical outcome.Neoplasia (New York, N.Y.) · 2015Article
- The importance of being dead: cell death mechanisms assessment in anti-sarcoma therapy.Frontiers in oncology · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeUterine leiomyosarcoma (ULMS) is a poorly understood cancer with few effective treatments. This study explores the molecular events involved in ULMS with the goal of developing novel therapeutic strategies. EXPERIMENTAL
designGenome-wide transcriptional profiling, Western blotting, and real-time PCR were used to compare specimens of myometrium, leiomyoma, and leiomyosarcoma. Aurora A kinase was targeted in cell lines derived from metastatic ULMS using siRNA or MK-5108, a highly specific small-molecule inhibitor. An orthotopic model was used to evaluate the ability of MK-5108 to inhibit ULMS growth in vivo.
resultsWe found that 26 of 50 gene products most overexpressed in ULMS regulate mitotic centrosome and spindle functions. These include UBE2C, Aurora A and B kinase, TPX2, and Polo-like kinase 1 (PLK1). Targeting Aurora A inhibited proliferation and induced apoptosis in LEIO285, LEIO505, and SK-LMS1, regardless of whether siRNA or MK-5108 was used. In vitro, MK-5108 did not consistently synergize with gemcitabine or docetaxel. Gavage of an orthotopic ULMS model with MK-5108 at 30 or 60 mg/kg decreased the number and size of tumor implants compared with sham-fed controls. Oral MK-5108 also decreased the rate of proliferation, increased intratumoral apoptosis, and increased expression of phospho-histone H3 in ULMS xenografts.
conclusionsOur results show that dysregulated centrosome function and spindle assembly are a robust feature of ULMS that can be targeted to slow its growth both in vitro and in vivo. These observations identify novel directions that can be potentially used to improve clinical outcomes for this disease.
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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.