ArticlePLoS biology2023
Combating castration-resistant prostate cancer by co-targeting the epigenetic regulators EZH2 and HDAC.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Circulating Tumor DNA as Emerging Predictive and Prognostic Biomarker in Prostate Cancer.Cancers · 2026Review
- EZH2 Suppression Diversifies Prostate Cancer Lineage Variant Evolution and Lacks Efficacy in Inhibiting Disease Progression.Cancer research · 2026Article
- Androgen receptor reactivation in castration-resistant prostate cancer: mechanisms, epigenetic adaptation, and therapeutic vulnerabilities.Frontiers in oncology · 2026Review
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- Precision epigenetic therapies in oncology.Cancer metastasis reviews · 2025Review
- Molecular mechanisms and clinical insights in transformed small cell lung cancer: a narrative review.Translational lung cancer research · 2025Review
- EZH2 inhibitor SHR2554 enhances the anti-tumor efficacy of HDAC inhibitor Chidamide through STAT1 in T-cell lymphoma.Cell death & disease · 2025Article
- Review
- An update on the tumor-suppressive functions of the RasGAP protein DAB2IP with focus on therapeutic implications.Cell death and differentiation · 2024Review
- Review
- Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review.Cancers · 2024Review
- Intermediate risk prostate tumors contain lethal subtypes.Frontiers in urology · 2024Article
- What should be the future direction of development in the field of prostate cancer with lung metastasis?World journal of clinical oncology · 2023Article
- Combining EZH2 and HDAC inhibitors to target castration-resistant prostate cancers.PLoS biology · 2023Article
- The contemporary management of prostate cancer.CA: a cancer journal for cliniciansReview
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
While screening and early detection have reduced mortality from prostate cancer, castration-resistant disease (CRPC) is still incurable. Here, we report that combined EZH2/HDAC inhibitors potently kill CRPCs and cause dramatic tumor regression in aggressive human and mouse CRPC models. Notably, EZH2 and HDAC both transmit transcriptional repressive signals: regulating histone H3 methylation and histone deacetylation, respectively. Accordingly, we show that suppression of both EZH2 and HDAC are required to derepress/induce a subset of EZH2 targets, by promoting the sequential demethylation and acetylation of histone H3. Moreover, we find that the induction of one of these targets, ATF3, which is a broad stress response gene, is critical for the therapeutic response. Importantly, in human tumors, low ATF3 levels are associated with decreased survival. Moreover, EZH2- and ATF3-mediated transcriptional programs inversely correlate and are most highly/lowly expressed in advanced disease. Together, these studies identify a promising therapeutic strategy for CRPC and suggest that these two major epigenetic regulators buffer prostate cancers from a lethal response to cellular stresses, thereby conferring a tractable therapeutic vulnerability.
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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.