ArticleOncotarget2016
Inhibition of EZH2 by chemo- and radiotherapy agents and small molecule inhibitors induces cell death in castration-resistant prostate cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.Prostate cancer and prostatic diseases · 2020Pooled it
- Targeting DNA Topoisomerase I for the Treatment of Cancer: Past, Present and Future.Journal of molecular biology · 2026Review
- Post-translational modification networks in tumor radiosensitivity: mechanistic insights and therapeutic opportunities.Journal of translational medicine · 2026Review
- Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors.Annals of medicine · 2023Review
- Simultaneous administration of EZH2 and BET inhibitors inhibits proliferation and clonogenic ability of metastatic prostate cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- The clinicopathological and prognostic significances of EZH2 expression in urological cancers: A meta‑analysis and bioinformatics analysis.Oncology letters · 2023Article
- DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.International journal of molecular sciences · 2022Review
- Review
- From Therapy Resistance to Targeted Therapies in Prostate Cancer.Frontiers in oncology · 2022Review
- Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression.Nature communications · 2021Article
- LINC00662 Promotes Oral Squamous Cell Carcinoma Cell Growth and Metastasis through miR-144-3p/EZH2 Axis.Yonsei medical journal · 2021Article
- Roles of Key Epigenetic Regulators in the Gene Transcription and Progression of Prostate Cancer.Frontiers in molecular biosciences · 2021Review
- Comprehensive Analysis of the Expression Characteristics of the Enhancer of the Zeste Homolog 2 Gene in Pan-Cancer.Frontiers in genetics · 2021Article
- [Effect of enhancer of zeste homolog 2 inhibitor GSK126 on the proliferation and apoptosis of tongue squamous cell carcinoma].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2020Article
- HNF1B, EZH2 and ECI2 in prostate carcinoma. Molecular, immunohistochemical and clinico-pathological study.Scientific reports · 2020Article
- Resolving DNA Damage: Epigenetic Regulation of DNA Repair.Molecules (Basel, Switzerland) · 2020Review
- Combining epigenetic drugs with other therapies for solid tumours - past lessons and future promise.Nature reviews. Clinical oncology · 2020Review
- Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy.The Prostate · 2019Article
- Dysregulated Transcriptional Control in Prostate Cancer.International journal of molecular sciences · 2019Review
- The histone methyltransferase WHSC1 is regulated by EZH2 and is important for ovarian clear cell carcinoma cell proliferation.BMC cancer · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Androgen deprivation therapy is the mainstay of treatment of advanced prostate cancer (PCa). However, a significant portion of patients experience disease relapse and tumors ultimately evolve into castration resistant prostate cancer (CRPC), for which there is no cure in the clinic. The Polycomb protein enhancer of zeste homolog 2 (EZH2) is frequently overexpressed in CRPC. It is unclear whether EZH2 can be a therapeutic target in CRPC. Here, we demonstrated that chemo- and radiotherapy agents such as camptothecin (CPT) and γ irradiation decrease EZH2 expression in various PCa cell lines. We provided evidence that functional p53 and RB proteins are required for CPT- and irradiation-induced downregulation of EZH2 in CRPC cells. We demonstrated that EZH2-specific small molecule inhibitors mitigate CRPC cell growth. We further showed that the EZH2 inhibitor GSK126 inhibits both Polycomb-dependent and -independent functions of EZH2 in PCa cells. Importantly, we found that inhibition of EZH2 by genetic and pharmacological means sensitizes CRPC cells to CPT-induced apoptotic death and growth inhibition in culture and in mice. Our data suggest that concomitant administration of small molecule inhibitors of EZH2 may significantly increase the anti-tumor efficacy of conventional chemo- and radiotherapies in CRPC.
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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.