Evidence map›Paper›PMID 39117665›Full record

ArticleNature communications2024

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes.

Varadha Balaji Venkadakrishnan, Adam G Presser, Richa Singh, Matthew A Booker, Nicole A Traphagen, Kenny Weng, Nathaniel C E Voss, Navin R Mahadevan, Kei Mizuno, Loredana Puca and 10 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing 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

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

  1. Pooled it
  2. Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026
    Review
  3. Review
  4. Review
  5. [A multi-level study of androgen deprivation therapy on the immune microenvironment in prostate cancer].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026
    Article
  6. EZH2 Inhibition and Myeloid Risk: A Feature of On-Target Biology.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  7. Article
  8. B7-H3 Gene Expression Shapes Prognosis and Therapeutic Opportunities across Patient Groups with Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  9. Article
  10. Article
  11. Tumor-Associated Macrophage Exosomal miR-142-5p Drives Prostate Cancer Neuroendocrine Differentiation via RERG/Ras/ERK Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  12. Review
  13. Article
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  19. Article
  20. Article

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Varadha Balaji VenkadakrishnanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-7071-4584
Adam G PresserDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Richa SinghDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Matthew A BookerDepartment of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA, USA.
Nicole A TraphagenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kenny WengDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0009-0000-4813-5308
Nathaniel C E VossDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Navin R MahadevanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kei MizunoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Loredana PucaDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Osasenaga IdahorDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sheng-Yu KuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-4715-1888
Martin K BakhtDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-8803-2485
Ashir A BorahThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-1193-4987
Zachary T HerbertMolecular Biology Core Facilities, Dana-Farber Cancer Institute, Boston, MA, USA.
Michael Y TolstorukovDepartment of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-9134-8808
David A BarbieDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
David S RickmanDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0001-7420-5883
Myles BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-8213-1658
Himisha BeltranDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. himisha_beltran@dfci.harvard.edu.ORCID 0000-0003-3259-2226

Funding

Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0M
Molecular Determinants of Response and Resistance to EZH2 and PARP inhibition in Prostate CancerP50CA272390 · NCI · DANA-FARBER CANCER INST · PI Steven P. Balk, Himisha Beltran · 2023 to 2026
$12.0M
Weill Cornell Medicine (WCM) SPORE in Prostate CancerP50CA211024 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI GUDAS, LORRAINE J · 2017 to 2021
$10.9M
Molecular mechanisms underlying lineage plasticity in prostate cancerR37CA241486 · NCI · DANA-FARBER CANCER INST · PI Himisha Beltran · 2020 to 2026
$4.1M
"DNMT and TET1 reprogramming as a targetable mechanism of resistance in advanced prostate cancer"R01CA274963 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI Himisha Beltran, David S. Rickman · 2023 to 2026
$2.6M
Defining Molecular Determinants of Lineage Plasticity as a Mechanism of Treatment Resistance in Prostate CancerR01CA230913 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI RICKMAN, DAVID S. · 2019 to 2023
$2.2M
Young Empowered Scientists for ContinUed Research Engagement (YES for CURE)R25CA221738 · NCI · DANA-FARBER CANCER INST · PI DECAPRIO, JAMES A. · 2017 to 2023
$2.1M
NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA211024NCI NIH HHS P50 CA272390NCI NIH HHS R01 CA230913NCI NIH HHS R01 CA274963NCI NIH HHS R25 CA221738NCI NIH HHS R37 CA241486U.S. Department of Defense (United States Department of Defense) W81XWH-17-1-0653U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) WCM SPORE P50 CA211024-01A1
6 · The paper itself

Abstract

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and emerging therapeutic target that is overexpressed in most castration-resistant prostate cancers and implicated as a driver of disease progression and resistance to hormonal therapies. Here we define the lineage-specific action and differential activity of EZH2 in both prostate adenocarcinoma and neuroendocrine prostate cancer (NEPC) subtypes of advanced prostate cancer to better understand the role of EZH2 in modulating differentiation, lineage plasticity, and to identify mediators of response and resistance to EZH2 inhibitor therapy. Mechanistically, EZH2 modulates bivalent genes that results in upregulation of NEPC-associated transcriptional drivers (e.g., ASCL1) and neuronal gene programs in NEPC, and leads to forward differentiation after targeting EZH2 in NEPC. Subtype-specific downstream effects of EZH2 inhibition on cell cycle genes support the potential rationale for co-targeting cyclin/CDK to overcome resistance to EZH2 inhibition.

Indexed as

Enhancer of Zeste Homolog 2 ProteinGene Expression Regulation, NeoplasticProstatic NeoplasmsAdenocarcinomaAnimalsCell DifferentiationCell LineageCell Line, TumorDrug Resistance, NeoplasmHumansMaleMiceProstatic Neoplasms, Castration-ResistantEnhancer of Zeste Homolog 2 ProteinEZH2 protein, human

Identifiers

PMID39117665
PMCPMC11310309

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.