ArticleOncotarget2015
Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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
68 citing papers in PubMed, 97 citations in OpenAlex.
- Phase I/II Study of the CDK2/9 Inhibitor Fadraciclib in Combination with Chemotherapy in Children with Advanced Malignancies: Arm K of the AcSé-ESMART Trial.Targeted oncology · 2026Trial
- Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma.Cancer medicine · 2023Trial
- Targeted and molecular therapies in Ewing sarcoma: a comprehensive review of preclinical and clinical advances.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Combined inhibition of CDK4/6 and PI3K pathways exhibit highly synergistic activity and translational potential in Ewing sarcoma.Translational oncology · 2026Article
- The hegemonic EWSR1::ETS oncoprotein overrules core regulatory circuitry principles in Ewing sarcoma.NPJ precision oncology · 2025Article
- Enhancer regulation in cancer: from epigenetics to mArchives of pharmacal research · 2025Review
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- Revisiting CDKN2A dysregulation in Ewing sarcoma.Molecular oncology · 2025Article
- Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies.Journal of translational medicine · 2025Review
- Super-enhancer DNA methylation in cancer: the mechanism of action and therapeutic directions.Frontiers in oncology · 2025Review
- Current progress and future perspective of super-enhancers: a viable and effective bridge between the transcriptional apparatus and disease.Frontiers in genetics · 2025Review
- Primary Bone Tumors and Breast Cancer-Induced Bone Metastases: In Vivo Animal Models and New Alternative Approaches.Biomedicines · 2024Review
- Article
- EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumors.Nature communications · 2024Article
- EWS-FLI1 and Activator Protein-1 (AP-1) Reciprocally Regulate Extracellular-Matrix Proteins in Ewing sarcoma Cells.International journal of molecular sciences · 2024Article
- ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3.Molecular cancer research : MCR · 2024Article
- Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors.Cancer research · 2024Article
- Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.International journal of molecular sciences · 2024Review
- Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics.Frontiers in cell and developmental biology · 2024Review
- ETS1, a target gene of the EWSR1::FLI1 fusion oncoprotein, regulates the expression of the focal adhesion protein TENSIN3.bioRxiv : the preprint server for biology · 2023Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Ewing sarcoma is an aggressive bone and soft tissue tumor in children and adolescents, with treatment remaining a clinical challenge. This disease is mediated by somatic chromosomal translocations of the EWS gene and a gene encoding an ETS transcription factor, most commonly, FLI1. While direct targeting of aberrant transcription factors remains a pharmacological challenge, identification of dependencies incurred by EWS/FLI1 expression would offer a new therapeutic avenue. We used a combination of super-enhancer profiling, near-whole genome shRNA-based and small-molecule screening to identify cyclin D1 and CDK4 as Ewing sarcoma-selective dependencies. We revealed that super-enhancers mark Ewing sarcoma specific expression signatures and EWS/FLI1 target genes in human Ewing sarcoma cell lines. Particularly, a super-enhancer regulates cyclin D1 and promotes its expression in Ewing sarcoma. We demonstrated that Ewing sarcoma cells require CDK4 and cyclin D1 for survival and anchorage-independent growth. Additionally, pharmacologic inhibition of CDK4 with selective CDK4/6 inhibitors led to cytostasis and cell death of Ewing sarcoma cell lines in vitro and growth delay in an in vivo Ewing sarcoma xenograft model. These results demonstrated a dependency in Ewing sarcoma on CDK4 and cyclin D1 and support exploration of CDK4/6 inhibitors as a therapeutic approach for patients with this disease.
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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.