Evidence map›Paper›PMID 40221372›Full record

ArticleEuropean urology focus2025

Reprogramming of Androgen Receptor Activity in Castration-resistant Prostate Cancer is Shaped by Truncated Variants.

Mitchell G Lawrence, Shivakumar Keerthikumar, Scott L Townley, Ashlee K Clark, Georgia B Cuffe, Geraldine Laven-Law, Adrienne R Hanson, Raj K Shrestha, Todd P Knutson, Michelle G Richards and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology focus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Mitchell G LawrenceDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Cabrini Institute, Cabrini Health, Malvern, Australia; Melbourne Urological Research Alliance, Monash University, Clayton, Australia. Electronic address: mitchell.lawrence@monash.edu.
Shivakumar KeerthikumarDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
Scott L TownleyFlinders University College of Medicine and Public Health, Flinders Health and Medical Research Institute, Bedford Park, Australia.
Ashlee K ClarkDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Georgia B CuffeDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Geraldine Laven-LawFlinders University College of Medicine and Public Health, Flinders Health and Medical Research Institute, Bedford Park, Australia; Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, Australia.
Adrienne R HansonFlinders University College of Medicine and Public Health, Flinders Health and Medical Research Institute, Bedford Park, Australia.
Raj K ShresthaFlinders University College of Medicine and Public Health, Flinders Health and Medical Research Institute, Bedford Park, Australia.
Todd P KnutsonMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA.
Michelle G RichardsDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Linda TengDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Nicholas ChooDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Megan CrumbakerGarvan Institute of Medical Research, Sydney, Australia; St. Vincent's Clinical School, UNSW Australia, Sydney, Australia; The Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, Australia.
Anthony M JoshuaGarvan Institute of Medical Research, Sydney, Australia; St. Vincent's Clinical School, UNSW Australia, Sydney, Australia; The Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, Australia.
Eva CoreyDepartment of Urology, University of Washington, Seattle, WA, USA.
Peter S NelsonDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Scott M DehmMasonic Cancer Center and Departments of Laboratory Medicine and Pathology and of Urology, University of Minnesota, Minneapolis, MN, USA.
Gail P RisbridgerDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Cabrini Institute, Cabrini Health, Malvern, Australia; Melbourne Urological Research Alliance, Monash University, Clayton, Australia.
Wayne D TilleyDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, Australia.
Theresa E HickeyDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, Australia.
Renea A TaylorPeter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Cabrini Institute, Cabrini Health, Malvern, Australia; Melbourne Urological Research Alliance, Monash University, Clayton, Australia; Department of Physiology, Biomedicine Discovery Institute Cancer Program, Monash University, Clayton, Australia.
Luke A SelthFlinders University College of Medicine and Public Health, Flinders Health and Medical Research Institute, Bedford Park, Australia; Freemasons Centre for Male Health and Wellbeing, Flinders University, Bedford Park, Australia; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia. Electronic address: luke.selth@flinders.edu.au.

Funding

TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0M
AR Gene Rearrangements and AR Signaling in Prostate CancerR01CA174777 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2013 to 2026
$4.9M
Clinical genomic predictive model of first line androgen receptor inhibitor therapy outcomes in men with mCRPCR01CA256157 · NCI · DUKE UNIVERSITY · PI ARMSTRONG, ANDREW J, DEHM, SCOTT M. · 2020 to 2025
$3.2M
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
Targeting early events in prostate cancer lineage plasticityR01CA270539 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2023 to 2026
$1.8M
NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA174777NCI NIH HHS R01 CA234715NCI NIH HHS R01 CA256157NCI NIH HHS R01 CA270539
6 · The paper itself

Abstract

BACKGROUND AND

objectiveUnder the selective pressure of treatment, prostate cancer cells express constitutively active androgen receptor (AR) variants. Whether AR variants mediate therapy resistance remains contested, because they are often coexpressed with abundant full-length AR. Therefore, we sought to determine how truncated variants shape AR chromatin occupancy and responses to treatments in both the presence and absence of full-length AR.

methodsWe used a cohort of patient-derived xenografts of metastatic prostate cancer with diverse AR alterations. Chromatin immunoprecipitation and RNA sequencing were used to compare the landscape of AR binding and transcriptomic features. We assessed responses to castration by castrating host mice and evaluated responses to bipolar androgen therapy by administering testosterone cypionate. KEY FINDINGS AND LIMITATIONS: By profiling the AR cistrome, we identified a distinct group of tumours defined by ARv567es expression, a variant arising due to structural rearrangements of the AR gene. ARv567es-positive tumours also had a distinct epigenomic profile and altered transcriptional features, including loss of canonical AR-regulated gene signatures and elevated expression of AR-repressed genes. ARv567es-positive tumours were resistant to castration and bipolar androgen therapy. In tumours that coexpress full-length AR, this involves dampened transcriptional responses and disruption of the autoregulatory loop that modulates AR levels. Study limitations include the need for additional models of AR-driven prostate cancer. CONCLUSIONS AND CLINICAL IMPLICATIONS: The emergence of ARv567es via gene rearrangements causes transcriptional reprogramming and therapy resistance. This highlights ARv567es as a potential as a marker to guide treatment decisions.

Indexed as

Prostatic Neoplasms, Castration-ResistantReceptors, AndrogenAnimalsGene Expression Regulation, NeoplasticHumansMaleMiceAR protein, humanReceptors, AndrogenAndrogen deprivation therapyAndrogen receptorBipolar androgen therapyChromatin immunoprecipitationCistromePatient-derived xenograftProstate cancer

Identifiers

PMID40221372
PMCPMC13180466

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.