Evidence map›Paper›PMID 33462444›Full record

ArticleNature medicine2021

The androgen receptor is a tumor suppressor in estrogen receptor-positive breast cancer.

Theresa E Hickey, Luke A Selth, Kee Ming Chia, Geraldine Laven-Law, Heloisa H Milioli, Daniel Roden, Shalini Jindal, Mun Hui, Jessica Finlay-Schultz, Esmaeil Ebrahimie and 14 more

Open access · bronzeAbstract read
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In one paragraph

Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed, 1 pooled it
35.5field-weighted citation impact, top 1% of its field
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

153 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 11 institutions in 5 countries.

Theresa E HickeyDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.ORCID http://orcid.org/0000-0002-2752-730X
Luke A SelthDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Kee Ming ChiaGarvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
Geraldine Laven-LawDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.ORCID http://orcid.org/0000-0001-5326-1931
Heloisa H MilioliGarvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-5104-487X
Daniel RodenGarvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-2393-5805
Shalini JindalDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Mun HuiGarvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
Jessica Finlay-SchultzUniversity of Colorado, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-7855-9870
Esmaeil EbrahimieDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.ORCID http://orcid.org/0000-0003-1699-3476
Stephen N BirrellDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.ORCID http://orcid.org/0000-0002-1023-413X
Suzan StellooOncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Richard IggoDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.ORCID http://orcid.org/0000-0002-8822-9111
Sarah AlexandrouGarvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-1186-6507
C Elizabeth CaldonGarvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-1392-3472
Tarek M Abdel-FatahUniversity of Nottingham, Nottingham, UK.
Ian O EllisUniversity of Nottingham, Nottingham, UK.
Wilbert ZwartOncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-9823-7289
Carlo PalmieriInstitute of Systems, Molecular and Integrative Biology, University of Liverpool & Clatterbridge Centre NHS Foundation Trust, Liverpool, UK.
Carol A SartoriusUniversity of Colorado, Aurora, CO, USA.
Alex SwarbrickGarvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-3051-5676
Elgene LimGarvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-8065-8838
Jason S CarrollCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-3643-0080
Wayne D TilleyDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. wayne.tilley@adelaide.edu.au.ORCID http://orcid.org/0000-0003-1893-2626
Garvan Institute of Medical Research · AUThe University of Adelaide · AUUniversity of Colorado Anschutz Medical Campus · USUniversity of Nottingham · GBFlinders University · AUFreemasons Foundation Centre for Men's Health · AURadboud University Nijmegen · NLThe Netherlands Cancer Institute · NLUniversité de Bordeaux · FRUniversity of Cambridge · GBUniversity of Liverpool · GB

Funding

Hormones and Tumor Initiating Cells in Human Breast CancersR01CA140985 · NCI · UNIVERSITY OF COLORADO DENVER · PI SARTORIUS, CAROL ANN · 2011 to 2020
$3.0M
Cancer Research UK 20411NCI NIH HHS R01 CA140985
6 · The paper itself

Abstract

The role of the androgen receptor (AR) in estrogen receptor (ER)-α-positive breast cancer is controversial, constraining implementation of AR-directed therapies. Using a diverse, clinically relevant panel of cell-line and patient-derived models, we demonstrate that AR activation, not suppression, exerts potent antitumor activity in multiple disease contexts, including resistance to standard-of-care ER and CDK4/6 inhibitors. Notably, AR agonists combined with standard-of-care agents enhanced therapeutic responses. Mechanistically, agonist activation of AR altered the genomic distribution of ER and essential co-activators (p300, SRC-3), resulting in repression of ER-regulated cell cycle genes and upregulation of AR target genes, including known tumor suppressors. A gene signature of AR activity positively predicted disease survival in multiple clinical ER-positive breast cancer cohorts. These findings provide unambiguous evidence that AR has a tumor suppressor role in ER-positive breast cancer and support AR agonism as the optimal AR-directed treatment strategy, revealing a rational therapeutic opportunity.

Indexed as

AndrogensBreast NeoplasmsCell Line, TumorCell ProliferationCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Estrogen Receptor alphaFemaleHumansMCF-7 CellsNuclear Receptor Coactivator 3Receptors, AndrogenSignal TransductionAndrogensAR protein, humanCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Estrogen Receptor alphaNCOA3 protein, humanNuclear Receptor Coactivator 3Receptors, Androgen

Identifiers

PMID33462444
OpenAlexW3124502889

What OpenQuestion holds

Textmetadata
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.