ArticleOncotarget2015
Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
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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
37 citing papers in PubMed, 58 citations in OpenAlex.
- Hesperidin and Hesperetin: Epigenetic-Stemness Crosstalk, Antitumor Mechanisms, Preclinical Data and Translation Barriers.Biomolecules · 2026Review
- SMURF2 in Anticancer Therapy: Dual Role in Carcinogenesis and Theranostics.International journal of molecular sciences · 2026Review
- Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review.Life (Basel, Switzerland) · 2024Review
- Identification of circadian clock-related immunological prognostic index and molecular subtypes in prostate cancer.Discover oncology · 2024Article
- Expression and biological significance of topoisomerase II α (TOP2A) in oral squamous cell carcinoma.Discover oncology · 2024Article
- Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review.Cancers · 2024Review
- Phenotypic Plasticity - Alternate Transcriptional Programs Driving Treatment Resistant Prostate Cancer.Critical reviews in oncogenesis · 2022Review
- Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression.Nature communications · 2021Article
- Implications of prognosis-associated genes in pancreatic tumor metastasis: lessons from global studies in bioinformatics.Cancer metastasis reviews · 2021Review
- Novel insights into the interaction between long non-coding RNAs and microRNAs in glioma.Molecular and cellular biochemistry · 2021Review
- MiRNA-145-5p expression and prospective molecular mechanisms in the metastasis of prostate cancer.IET systems biology · 2021Article
- Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication.Frontiers in genetics · 2021Article
- Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.International journal of molecular sciences · 2020Article
- Transcriptome analysis reveals key signature genes involved in the oncogenesis of lung cancer.Cancer biomarkers : section A of Disease markers · 2020Article
- Prognostic value of TOP2A in bladder urothelial carcinoma and potential molecular mechanisms.BMC cancer · 2019Article
- Pharmacological inhibition of EZH2 combined with DNA‑damaging agents interferes with the DNA damage response in MM cells.Molecular medicine reports · 2019Article
- Patient derived organoids to model rare prostate cancer phenotypes.Nature communications · 2018Article
- Recent Advances in Prostate Cancer Treatment and Drug Discovery.International journal of molecular sciences · 2018Review
- Expression of EZH2 is associated with poor outcome in colorectal cancer.Oncology letters · 2018Article
- STAT5BN642H is a driver mutation for T cell neoplasia.The Journal of clinical investigation · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Progression of aggressive prostate cancers (PCa) with androgen receptor splice variants or neuroendrocrine features is currently untreatable in the clinic. Therefore novel therapies are urgently required. We conducted RNA-seq using tumors from a unique murine transplant mouse model which spontaneously progresses to metastatic disease. Differential gene expression analysis revealed a significant increase of topoisomerase IIα, Top2a (Top2a) in metastatic tumors. Interrogation of human data revealed that increased Top2a expression in primary tumors selected patients with more aggressive disease. Further, significant positive correlation was observed between Top2a and the histone methyltransferase, Ezh2. Combination of the Top2 poison etoposide with the Ezh2 inhibitor GSK126 or DZNep significantly increased cell death in vitro in murine and human prostate cancer cell lines. Additionally, combination therapy extended time to progression and increased therapeutic efficacy in vivo. Overall, our studies demonstrate that patients screened for Top2a and Ezh2 expression would exhibit significant response to a combinational treatment involving low dose etoposide combined with Ezh2 inhibition. In addition, our data suggests that this combination therapeutic strategy is beneficial against aggressive PCa, and provides strong rationale for continued clinical development.
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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.