Evidence map›Paper›PMID 40609538›Full record

Trial reportCell reports. Medicine2025

Epigenetic profiling identifies markers of endocrine resistance and therapeutic options for metastatic castration-resistant prostate cancer.

Tesa M Severson, Emma Minnee, Yanyun Zhu, Karianne Schuurman, Holly M Nguyen, Lisha G Brown, Sini Hakkola, Renee Menezes, Sebastian Gregoricchio, Yongsoo Kim and 21 more

Abstract readClinical Trial, Phase II
In one paragraph

Trial report in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. ANXA2-mediated Phagocytosis Generates ARAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Epigenetic (De)regulation in Prostate Cancer.Cancer treatment and research · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors.

Tesa M SeversonDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands; Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Emma MinneeDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands.
Yanyun ZhuDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands.
Karianne SchuurmanDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Holly M NguyenDepartment of Urology, University of Washington, Seattle, WA 98195, USA.
Lisha G BrownDepartment of Urology, University of Washington, Seattle, WA 98195, USA.
Sini HakkolaProstate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, 33100 Tampere, Finland.
Renee MenezesBiostatistics Centre & Department of Psychosocial Research and Epidemiology, the Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Sebastian GregoricchioDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands.
Yongsoo KimDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Jeroen KneppersDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands.
Simon LinderDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands.
Suzan StellooDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands.
Cor LieftinkDivision of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Michiel S van der HeijdenDivision of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Division of Medical Oncology, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Matti NykterProstate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, 33100 Tampere, Finland.
Vincent van der NoortDepartment of Biometrics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Joyce SandersDepartment of Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Ben MorrisDivision of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Guido JensterDepartment of Urology, Erasmus MC, 3015 GD Rotterdam, the Netherlands.
Geert Jlh van LeendersDepartment of Pathology, Erasmus MC Cancer Institute, 3015 CP Rotterdam, the Netherlands.
Mark PomerantzDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Matthew L FreedmanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA.
Roderick L BeijersbergenDivision of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Alfonso UrbanucciProstate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, 33100 Tampere, Finland; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway.
Lodewyk WesselsCancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands; Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Department of EEMCS, Delft University of Technology, 2628 CM Delft, the Netherlands.
Peter S NelsonDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA 98195, USA.
Eva CoreyDepartment of Urology, University of Washington, Seattle, WA 98195, USA.
Stefan PrekovicDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands.
Wilbert ZwartDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands; Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands. Electronic address: w.zwart@nki.nl.
Andries M BergmanDivision of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Division of Medical Oncology, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. Electronic address: a.bergman@nki.nl.

Funding

Defining and Targeting Lineage Transition Programs Operative in AR Pathway Independent Prostate CancerR01CA234715 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NELSON, PETER S · 2020 to 2024
$2.0M
NCI NIH HHS R01 CA234715
6 · The paper itself

Abstract

Androgen receptor (AR) signaling inhibitors, including enzalutamide, are treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), but resistance inevitably develops. Using metastatic samples from a prospective phase 2 clinical trial, we epigenetically profile enhancer/promoter activities with acetylation of lysine residue 27 on histone 3 (H3K27ac) chromatin immunoprecipitation followed by sequencing, before and after AR-targeted therapy. We identify a distinct subset of H3K27ac-differentially marked regions that are associated with treatment responsiveness, which we successfully validate in mCRPC patient-derived xenograft (PDX) models. In silico analyses reveal histone deacetylase (HDAC)3 to critically drive resistance to hormonal interventions, which we validate in vitro. Critically, we identify the pan-HDAC inhibitor vorinostat to be effective in decreasing tumor cell proliferation, both in vitro and in vivo. Moreover, we uncover evidence for HDAC3 working together with glucocorticoid receptor (GR) as a potential mechanism for this therapeutic effect. These findings demonstrate the rationale for therapeutic strategies including HDAC inhibitors to improve patient outcome in advanced stages of mCRPC.

Indexed as

Biomarkers, TumorDrug Resistance, NeoplasmEpigenesis, GeneticProstatic Neoplasms, Castration-ResistantAcetylationAnimalsBenzamidesCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHistone Deacetylase 3Histone Deacetylase InhibitorsHistone DeacetylasesHistonesHumansMaleBenzamidesBiomarkers, TumorenzalutamideHistone Deacetylase 3Histone Deacetylase InhibitorsHistone DeacetylasesHistonesNitrilesPhenylthiohydantoinReceptors, AndrogenReceptors, GlucocorticoidVorinostatandrogen receptorbiomarkersdrug resistanceenzalutamideepigeneticsH3K27acHDAC inhibitorshormone interventionmCRPCprostate cancer

Identifiers

PMID40609538
PMCPMC12281433

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.