Evidence map›Paper›PMID 31931431›Full record

ArticleNeoplasia (New York, N.Y.)2020

Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment.

Steven Kregel, Chao Wang, Xin Han, Lanbo Xiao, Ester Fernandez-Salas, Pushpinder Bawa, Brooke L McCollum, Kari Wilder-Romans, Ingrid J Apel, Xuhong Cao and 3 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
9.1field-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

83 citing papers in PubMed, 140 citations in OpenAlex.

  1. Recent advances in hormone-based biopharmaceuticals for cancer therapy.Journal of the Egyptian National Cancer Institute · 2026
    Review
  2. A ligandable PNT domain establishes ERG as a directly targetable oncogenic driver in prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
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  9. Article
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  12. Androgen Signaling in Prostate Cancer: When a Friend Turns Foe.Endocrine, metabolic & immune disorders drug targets · 2025
    Review
  13. Metformin in overcoming enzalutamide resistance in castration-resistant prostate cancer.The Journal of pharmacology and experimental therapeutics · 2025
    Article
  14. Article
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  16. Review
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  20. Thiazole, Isatin and Phthalimide Derivatives TestedCurrent medicinal chemistry · 2024
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Steven KregelMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Chao WangDepartments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Xin HanDepartments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Lanbo XiaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ester Fernandez-SalasMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Pushpinder BawaMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Brooke L McCollumMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Kari Wilder-RomansDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Ingrid J ApelMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Xuhong CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Corey SpeersRogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Shaomeng WangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Arul M ChinnaiyanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: arul@umich.edu.
University of Michigan–Ann Arbor · USMichigan Center for Translational Pathology · USHoward Hughes Medical Institute · US

Funding

Tissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Timothy Dess · 2014 to 2026
$27.6M
Training Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3M
Exploring Precision Oncology: From Gene Fusions to lncRNAsR35CA231996 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2018 to 2024
$6.4M
Small-molecule degraders of BET proteinsR01CA215758 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WANG, SHAOMENG · 2017 to 2021
$3.1M
Targeting the MLL complex in Castration Resistant Prostate CancerR01CA200660 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, GREMBECKA, JOLANTA · 2016 to 2020
$1.9M
Howard Hughes Medical InstituteNCI NIH HHS P50 CA186786NCI NIH HHS R01 CA200660NCI NIH HHS R01 CA215758NCI NIH HHS R35 CA231996NCI NIH HHS T32 CA009676
6 · The paper itself

Abstract

Androgen receptor (AR) antagonists, such as enzalutamide, have had a major impact on the treatment of metastatic castration-resistant prostate cancer (CRPC). However, even with the advent of AR antagonist therapies, patients continue to develop resistance, and new strategies to combat continued AR signalling are needed. Here, we develop AR degraders using PROteolysis TArgeting Chimeric (PROTAC) technology in order to determine whether depletion of AR protein can overcome mechanisms of resistance commonly associated with current AR-targeting therapies. ARD-61 is the most potent of the AR degraders and effectively induces on-target AR degradation with a mechanism consistent with the PROTAC design. Compared to clinically-approved AR antagonists, administration of ARD-61 in vitro and in vivo results in more potent anti-proliferative, pro-apoptotic effects and attenuation of downstream AR target gene expression in prostate cancer cells. Importantly, we demonstrate that ARD-61 functions in enzalutamide-resistant model systems, characterized by diverse proposed mechanisms of resistance that include AR amplification/overexpression, AR mutation, and expression of AR splice variants, such as AR-V7. While AR degraders are unable to bind and degrade AR-V7, they continue to inhibit tumor cell growth in models overexpressing AR-V7. To further explore this, we developed several isogenic prostate cell line models in which AR-V7 is highly expressed, which also failed to influence the cell inhibitory effects of AR degraders, suggesting that AR-V7 is not a functional resistance mechanism for AR antagonism. These data provide compelling evidence that full-length AR remains a prominent oncogenic driver of prostate cancers which have developed resistance to AR antagonists and highlight the clinical potential of AR degraders for treatment of CRPC.

Indexed as

Androgen Receptor AntagonistsAndrogensAnimalsBenzamidesCell Line, TumorCell ProliferationDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansMaleMiceNitrilesPhenylthiohydantoinProstatic Neoplasms, Castration-ResistantReceptors, AndrogenXenograft Model Antitumor AssaysAndrogen Receptor AntagonistsAndrogensAR protein, humanBenzamidesenzalutamideNitrilesPhenylthiohydantoinReceptors, Androgen

Identifiers

PMID31931431
PMCPMC6957805
OpenAlexW2999280110

What OpenQuestion holds

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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 OpenQuestion graph.