Evidence map›Paper›PMID 25995342›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015

Antiandrogens Inhibit ABCB1 Efflux and ATPase Activity and Reverse Docetaxel Resistance in Advanced Prostate Cancer.

Yezi Zhu, Chengfei Liu, Cameron Armstrong, Wei Lou, Amandeep Sandher, Allen C Gao

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

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07172685 (Exploratory Study on the Efficacy and Safety of Triple Therapy), which is not on this map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.7field-weighted citation impact, top 5% 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.

NCT07172685 narecruitingnot on this mapstarted 2025, after this paper: background citation

Exploratory Study on the Efficacy and Safety of Triple Therapy (ADT + Darolutamide + Docetaxel Chemotherapy) Combined With Transrectal High-Intensity Focused Ultrasound Focal Therapy in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) With High Tumor Burden

TypeinterventionalSponsorQilu Hospital of Shandong UniversityRan2025 to 2027Enrolled116ConditionsProstate CancerArmsDarolutamide , Docetaxel , ADT and Transrectal HIFU Focal Therapy
3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 65 citations in OpenAlex.

  1. Trial
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  7. Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Article
  9. Review
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  14. Activation of theMolecular cancer therapeutics · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Yezi ZhuDepartment of Urology, University of California at Davis, Sacramento, California. Graduate Program in Pharmacology and Toxicology, University of California at Davis, Sacramento, California.
Chengfei LiuDepartment of Urology, University of California at Davis, Sacramento, California.
Cameron ArmstrongDepartment of Urology, University of California at Davis, Sacramento, California.
Wei LouDepartment of Urology, University of California at Davis, Sacramento, California.
Amandeep SandherDepartment of Urology, University of California at Davis, Sacramento, California.
Allen C GaoDepartment of Urology, University of California at Davis, Sacramento, California. Graduate Program in Pharmacology and Toxicology, University of California at Davis, Sacramento, California. Comprehensive Cancer Center, University of California at Davis, Sacramento, California. acgao@ucdavis.edu.
University of California, Davis · US

Funding

Novel roles of microRNA in androgen receptor signalingR01CA168601 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GAO, ALLEN C. · 2013 to 2017
$1.5M
Interleukin-6 and castration-resistant prostate cancerR01CA140468 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GAO, ALLEN C. · 2010 to 2014
$1.5M
(PQD-1) NF-kB activation and enzalutamide therapy in metastatic castration resistR21CA179970 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GAO, ALLEN C. · 2013 to 2014
$363k
Role of Rho GDP dissociation inhibitors in androgen signaling in prostate cancerI01BX000526 · VA · VA NORTHERN CALIFORNIA HEALTH CARE SYS · PI GAO, ALLEN C. · 2011 to 2013
–
BLRD VA I01 BX000526NCI NIH HHS CA140468NCI NIH HHS CA168601NCI NIH HHS CA179970NCI NIH HHS R01 CA140468NCI NIH HHS R01 CA168601NCI NIH HHS R21 CA179970
6 · The paper itself

Abstract

purposePrevious studies show that inhibition of ABCB1 expression overcomes acquired docetaxel resistance in C4-2B-TaxR cells. In this study, we examined whether antiandrogens, such as bicalutamide and enzalutamide, could inhibit ABCB1 activity and overcome resistance to docetaxel. EXPERIMENTAL

designABCB1 efflux activity was determined using a rhodamine efflux assay. ABCB1 ATPase activity was determined by Pgp-Glo assay systems. The effects of the antiandrogens bicalutamide and enzalutamide on docetaxel sensitivity were determined by cell growth assays and tumor growth in vivo.

resultsWe found that bicalutamide and enzalutamide inhibit ABCB1 ATP-binding cassette transporter activity through blocking ABCB1 efflux activity. Bicalutamide inhibited ABCB1 efflux activity by 40%, whereas enzalutamide inhibited ABCB1 efflux activity by approximately 60%. Both bicalutamide and enzalutamide inhibit ABCB1 ATPase activity. In addition, bicalutamide and enzalutamide inhibit ABCB1 efflux activity and desensitize docetaxel-resistant and androgen receptor (AR)-negative DU145 cells. Combination of bicalutamide with docetaxel had a significant antitumor effect in both AR-positive and AR-negative docetaxel-resistant xenograft models, suggesting that bicalutamide desensitizes docetaxel-resistant cells to docetaxel treatment independent of AR status.

conclusionsWe identified a novel mechanism of action for antiandrogens such as bicalutamide and enzalutamide as inhibitors of ABCB1 efflux and ATPase activity. Bicalutamide and enzalutamide desensitize docetaxel-resistant prostate cancer cells to docetaxel treatment independent of AR status. These studies may lead to the development of combinational therapies with bicalutamide/enzalutamide and docetaxel as effective regimens to treat advanced prostate cancer independent of AR status, and possibly other types of cancer.

Indexed as

Drug Resistance, NeoplasmAdenosine TriphosphatasesAdenosine TriphosphateAndrogen AntagonistsAnilidesAnimalsAntineoplastic Combined Chemotherapy ProtocolsATP Binding Cassette Transporter, Subfamily BBenzamidesCell Line, TumorDocetaxelGene Expression Regulation, NeoplasticHumansMaleMiceNitrilesABCB1 protein, humanAdenosine TriphosphatasesAdenosine TriphosphateAndrogen AntagonistsAnilidesAR protein, humanATP Binding Cassette Transporter, Subfamily BBenzamidesbicalutamideDocetaxelenzalutamideNitrilesPhenylthiohydantoinReceptors, AndrogenRhodaminesTaxoidsTosyl Compounds

Identifiers

PMID25995342
PMCPMC4573793
OpenAlexW2117490506

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.