Evidence map›Paper›PMID 27897170›Full record

ArticleNature communications2016

Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer.

Christine Henzler, Yingming Li, Rendong Yang, Terri McBride, Yeung Ho, Cynthia Sprenger, Gang Liu, Ilsa Coleman, Bryce Lakely, Rui Li and 10 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04015622 (A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone), which is not on this map. Cited by 112 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 3 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.

NCT04015622 phase2active not recruitingnot on this mapstarted 2020, after this paper: background citation

A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone

TypeinterventionalSponsorBritish Columbia Cancer AgencyRan2020 to 2026Enrolled100ConditionsMetastatic Castration-Resistant Prostate Cancer (mCRPC)ArmsEnzalutamide, Docetaxel
3 · Its place in the literature

Who cites it

112 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Evolution of AR and Non-AR Alterations in ctDNA of Patients with Metastatic Prostate Cancer Treated in the Phase III Alliance A031201 Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  9. Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
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52 more citing papers are in PubMed but not listed here.

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

20 authors.

Christine HenzlerMinnesota Supercomputing Institute, University of Minnesota, 117 Pleasant Street Southeast, Minneapolis, Minnesota 55455, USA.
Yingming LiMasonic Cancer Center, University of Minnesota, Mayo Mail Code 806, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455, USA.
Rendong YangMinnesota Supercomputing Institute, University of Minnesota, 117 Pleasant Street Southeast, Minneapolis, Minnesota 55455, USA.
Terri McBrideMasonic Cancer Center, University of Minnesota, Mayo Mail Code 806, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455, USA.ORCID http://orcid.org/0000-0002-9305-8038
Yeung HoMasonic Cancer Center, University of Minnesota, Mayo Mail Code 806, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455, USA.
Cynthia SprengerDivision of Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington 98104, USA.
Gang LiuDivision of Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington 98104, USA.
Ilsa ColemanFred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
Bryce LakelyDepartment of Urology, University of Washington, 1959 Northeast Pacific Street, Box 356510, Seattle, Washington 98195, USA.
Rui LiDepartment of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Shihong MaDepartment of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Sean R LandmanDepartment of Computer Science and Engineering, University of Minnesota, 200 Union Street Southeast, Minneapolis, Minnesota 55455, USA.
Vipin KumarDepartment of Computer Science and Engineering, University of Minnesota, 200 Union Street Southeast, Minneapolis, Minnesota 55455, USA.
Tae Hyun HwangQuantitative Biomedical Research Center, University of Texas Southwestern Medical Center, 2201 Inwood Road, Dallas, Texas 75390, USA.ORCID http://orcid.org/0000-0002-0389-5597
Ganesh V RajDepartment of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Celestia S HiganoFred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
Colm MorrisseyDepartment of Urology, University of Washington, 1959 Northeast Pacific Street, Box 356510, Seattle, Washington 98195, USA.
Peter S NelsonFred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
Stephen R PlymateDivision of Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington 98104, USA.
Scott M DehmMasonic Cancer Center, University of Minnesota, Mayo Mail Code 806, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455, USA.ORCID http://orcid.org/0000-0002-7827-5579

Funding

TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI John Kyung Lee · 2002 to 2026
$58.1M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Steven P. Balk · 2013 to 2026
$25.0M
Transmembrane Proteases and Prostate CarcinogenesisP01CA085859 · NCI · UNIVERSITY OF WASHINGTON · PI VESSELLA, ROBERT LOUIS · 2002 to 2013
$21.2M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008244 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SHIMIZU, YOJI · 1988 to 2024
$13.6M
AR Gene Rearrangements and AR Signaling in Prostate CancerR01CA174777 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2013 to 2026
$4.9M
Targeting the Metabolome in Androgen Receptor-driven Castration-resistant Prostate CancerI01BX003324 · VA · VA PUGET SOUND HEALTHCARE SYSTEM · PI PLYMATE, STEPHEN R. · 2016 to 2024
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BLRD VA I01 BX003324NCI NIH HHS P01 CA085859NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA174777NIGMS NIH HHS T32 GM008244
6 · The paper itself

Abstract

Molecularly targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signalling undermines therapeutic efficacy and promotes progression to lethal castration-resistant prostate cancer (CRPC), even when patients are treated with potent second-generation AR-targeted therapies abiraterone and enzalutamide. Here we define diverse AR genomic structural rearrangements (AR-GSRs) as a class of molecular alterations occurring in one third of CRPC-stage tumours. AR-GSRs occur in the context of copy-neutral and amplified AR and display heterogeneity in breakpoint location, rearrangement class and sub-clonal enrichment in tumours within and between patients. Despite this heterogeneity, one common outcome in tumours with high sub-clonal enrichment of AR-GSRs is outlier expression of diverse AR variant species lacking the ligand-binding domain and possessing ligand-independent transcriptional activity. Collectively, these findings reveal AR-GSRs as important drivers of persistent AR signalling in CRPC.

Indexed as

Genome, HumanAllelesCell Line, TumorChromosomes, Human, Pair 11Clone CellsExonsGene DosageGene Expression Regulation, NeoplasticGene RearrangementHumansMaleNeoplasm MetastasisProstatic Neoplasms, Castration-ResistantReceptors, AndrogenRNA, MessengerAR protein, humanReceptors, AndrogenRNA, Messenger

Identifiers

PMID27897170
PMCPMC5141345

What OpenQuestion holds

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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.