ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Aberrant Activation of Cell-Cycle-Related Kinases and the Potential Therapeutic Impact of PLK1 or CHEK1 Inhibition in Uterine Leiomyosarcoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Therapeutic Vulnerabilities of the Key Genetic Drivers in Leiomyosarcoma.Medical sciences (Basel, Switzerland) · 2026Review
- A Review of Proteomic Studies in Uterine Leiomyosarcoma: Biomarkers, Pathways, and Clinical Potential.Current issues in molecular biology · 2026Review
- Subtype-Specific Prognosis, Recurrence Patterns, and Molecular Features in 148 Chinese Uterine Sarcomas: A Real-World Study.Cancers · 2026Article
- TRIM47-facilitated PLK1 stabilization promotes the proliferation of liver cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Integrative bioinformatics analysis and experimental validation identify CHEK1 as an unfavorable prognostic biomarker related to immunosuppressive phenotypes in soft tissue sarcomas.NPJ precision oncology · 2025Article
- Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks.Medical oncology (Northwood, London, England) · 2025Article
- Development and validation of a novel signature to predict the survival and affect the immune microenvironment of esophageal squamous cell carcinoma: epigenetic-related genes.Frontiers in immunology · 2025Article
- Clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma.Orphanet journal of rare diseases · 2024Article
- Causal Effects of Oxidative Stress on Diabetes Mellitus and Microvascular Complications: Insights Integrating Genome-Wide Mendelian Randomization, DNA Methylation, and Proteome.Antioxidants (Basel, Switzerland) · 2024Article
- Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy.Cells · 2024Review
- CDCA5-EEF1A1 interaction promotes progression of clear cell renal cell carcinoma by regulating mTOR signaling.Cancer cell international · 2024Article
- Dysregulated Expression Patterns of Circular RNAs in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential.Biomolecules · 2024Review
- A bibliometric analysis of literatures on uterine leiomyosarcoma in the last 20 years.Frontiers in oncology · 2024Article
- Phase II Study of Olaparib and Temozolomide for Advanced Uterine Leiomyosarcoma (NCI Protocol 10250).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach.Oncology reports · 2023Article
- Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma.EMBO molecular medicine · 2023Article
- Therapeutic perspectives for adult soft tissue sarcoma-updates from the 2022 ASCO annual meeting.Cancer biology & medicine · 2022Article
- Comprehensive analysis of potential ceRNA network and immune cell infiltration in intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeUterine leiomyosarcoma is among the most aggressive gynecological malignancies. No effective treatment strategies have been established. This study aimed to identify novel therapeutic targets for uterine leiomyosarcoma based on transcriptome analysis and assess the preclinical efficacy of novel drug candidates. EXPERIMENTAL
designTranscriptome analysis was performed using fresh-frozen samples of six uterine leiomyosarcomas and three myomas. The Ingenuity Pathway Analysis (IPA) was used to identify potential therapeutic target genes for uterine leiomyosarcoma. Afterward, our results were validated using three independent datasets, including 40 uterine leiomyosarcomas. Then, the inhibitory effects of several selective inhibitors for the candidate genes were examined using SK-UT-1, SK-LMS-1, and SKN cell lines.
resultsWe identified 512 considerably dysregulated genes in uterine leiomyosarcoma compared with myoma. The IPA revealed that the function of several genes, including CHEK1 and PLK1, were predicted to be activated in uterine leiomyosarcoma. Through an in vitro drug screening, PLK1 or CHEK1 inhibitors (BI-2536 or prexasertib) were found to exert a superior anticancer effect against cell lines at low nanomolar concentrations and induce cell-cycle arrest. In SK-UT-1 tumor-bearing mice, BI-2536 monotherapy remarkably suppressed tumorigenicity. Moreover, the prexasertib and cisplatin combination therapy inhibited tumor proliferation and prolonged the time to tumor progression.
conclusionsWe identified upregulated expressions of PLK1 and CHEK1; their kinase activity was activated in uterine leiomyosarcoma. BI-2536 and prexasertib demonstrated a significant anticancer effect. Therefore, cell-cycle-related kinases may present a promising therapeutic strategy for the treatment of uterine leiomyosarcoma.
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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.