ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. 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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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Combined inhibition of CDK4/6 and PI3K pathways exhibit highly synergistic activity and translational potential in Ewing sarcoma.Translational oncology · 2026Article
- Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibition.Molecular therapy. Oncology · 2026Article
- Evaluating the causal effects of circulating plasma proteins on the risk of malignant neoplasms of bone and articular cartilage.The Journal of international medical research · 2026Article
- The Puzzle of Genetic Stability and Chromosomal Copy Number Alterations for the Therapy of Ewing Sarcoma.Cancers · 2025Review
- Article
- Focal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors.Molecular biology reports · 2025Review
- Therapeutic potential of isochlorogenic acid A fromFrontiers in immunology · 2025Article
- Causal effects of metabolites on malignant neoplasm of bone and articular cartilage: a mendelian randomization study.Frontiers in genetics · 2025Article
- Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research.Biomedicines · 2024Review
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Focal adhesion kinase: from biological functions to therapeutic strategies.Experimental hematology & oncology · 2023Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Regulation of EWSR1-FLI1 Function by Post-Transcriptional and Post-Translational Modifications.Cancers · 2023Review
- Ewing Sarcoma Meets Epigenetics, Immunology and Nanomedicine: Moving Forward into Novel Therapeutic Strategies.Cancers · 2022Review
- HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET.Journal of experimental & clinical cancer research : CR · 2022Article
- Epigenetic and Transcriptional Signaling in Ewing Sarcoma-Disease Etiology and Therapeutic Opportunities.Biomedicines · 2022Review
- Palbociclib-based high-throughput combination drug screening identifies synergistic therapeutic options in HPV-negative head and neck squamous cell carcinoma.BMC medicine · 2022Article
- Novel Targeted Therapeutic Strategies for Ewing Sarcoma.Cancers · 2022Review
- CircRPAP2 regulates the alternative splicing of PTK2 by binding to SRSF1 in breast cancer.Cell death discovery · 2022Article
- Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
Abstract
purposeEwing sarcoma is an aggressive solid tumor malignancy of childhood. Although current treatment regimens cure approximately 70% of patients with localized disease, they are ineffective for most patients with metastases or relapse. New treatment combinations are necessary for these patients. EXPERIMENTAL
designEwing sarcoma cells are dependent on focal adhesion kinase (FAK) for growth. To identify candidate treatment combinations for Ewing sarcoma, we performed a small-molecule library screen to identify compounds synergistic with FAK inhibitors in impairing Ewing cell growth. The activity of a top-scoring class of compounds was then validated across multiple Ewing cell lines
resultsNumerous Aurora kinase inhibitors scored as synergistic with FAK inhibition in this screen. We found that Aurora kinase B inhibitors were synergistic across a larger range of concentrations than Aurora kinase A inhibitors when combined with FAK inhibitors in multiple Ewing cell lines. The combination of AZD-1152, an Aurora kinase B-selective inhibitor, and PF-562271 or VS-4718, FAK-selective inhibitors, induced apoptosis in Ewing sarcoma cells at concentrations that had minimal effects on survival when cells were treated with either drug alone. We also found that the combination significantly impaired tumor progression in multiple xenograft models of Ewing sarcoma.
conclusionsFAK and Aurora kinase B inhibitors synergistically impair Ewing sarcoma cell viability and significantly inhibit tumor progression. This study provides preclinical support for the consideration of a clinical trial testing the safety and efficacy of this combination for patients with Ewing sarcoma.
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Registered trials
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