Evidence map›Paper›PMID 26483423›Full record

ArticleEndocrine-related cancer2016

Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer.

Jan Kroon, Martin Puhr, Jeroen T Buijs, Geertje van der Horst, Daniëlle M Hemmer, Koen A Marijt, Ming S Hwang, Motasim Masood, Stefan Grimm, Gert Storm and 4 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrine-related cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03863145 (Open Label, Multicenter, Phase 1 Study to Evaluate the Maximum Tolerated Dose of Orally Administered CB-03-10 With Dose Expansion Phase, in Subjects With Advanced Solid Tumors), which is not on this map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
6.5field-weighted citation impact, top 3% 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.

NCT03863145 early_phase1unknown statusnot on this mapstarted 2022, after this paper: background citation

Open Label, Multicenter, Phase 1 Study to Evaluate the Maximum Tolerated Dose of Orally Administered CB-03-10 With Dose Expansion Phase, in Subjects With Advanced Solid Tumors

TypeinterventionalSponsorCosmo Technologies LtdRan2022 to 2026Enrolled90ConditionsAdvanced Refractory Solid Tumors, Subjects Considered Likely to Respond to CB-03-10ArmsCB-03-10
3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 62 citations in OpenAlex.

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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

14 authors at 4 institutions in 3 countries.

Jan KroonDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands Department of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Martin PuhrDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Jeroen T BuijsDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Geertje van der HorstDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Daniëlle M HemmerDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Koen A MarijtDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Ming S HwangDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Motasim MasoodDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Stefan GrimmDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Gert StormDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands Department of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Josbert M MetselaarDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Onno C MeijerDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Zoran CuligDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands.
Gabri van der PluijmDepartment of UrologyLeiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Targeted TherapeuticsMIRA Institute for Biological Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDepartment of UrologyMedical University of Innsbruck, Innsbruck, AustriaDepartment of Clinical OncologyLeiden University Medical Center, Leiden, The NetherlandsDivision of Experimental MedicineImperial College London, London, UKDepartment of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsDepartment of EndocrinologyLeiden University Medical Center, Leiden, The Netherlands G.van_der_Pluijm@lumc.nl.
Leiden University Medical Center · NLImperial College London · GBInnsbruck Medical University · ATUniversity of Twente · NL

Funding

Austrian Science Fund FWF P 25639
6 · The paper itself

Abstract

Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. In this study, we aim to elucidate the role of the GR in docetaxel-resistant PCa in order to improve the current PCa therapies. GR expression was analyzed in a tissue microarray of primary PCa specimens from chemonaive and docetaxel-treated patients, and in cultured PCa cell lines with an acquired docetaxel resistance (PC3-DR, DU145-DR, and 22Rv1-DR). We found a robust overexpression of the GR in primary PCa from docetaxel-treated patients and enhanced GR levels in cultured docetaxel-resistant human PCa cells, indicating a key role of the GR in docetaxel resistance. The capability of the GR antagonists (RU-486 and cyproterone acetate) to revert docetaxel resistance was investigated and revealed significant resensitization of docetaxel-resistant PCa cells for docetaxel treatment in a dose- and time-dependent manner, in which a complete restoration of docetaxel sensitivity was achieved in both androgen receptor (AR)-negative and AR-positive cell lines. Mechanistically, we demonstrated down-regulation of Bcl-xL and Bcl-2 upon GR antagonism, thereby defining potential treatment targets. In conclusion, we describe the involvement of the GR in the acquisition of docetaxel resistance in human PCa. Therapeutic targeting of the GR effectively resensitizes docetaxel-resistant PCa cells. These findings warrant further investigation of the clinical utility of the GR antagonists in the management of patients with advanced and docetaxel-resistant PCa.

Indexed as

ApoptosisCyproterone AcetateDocetaxelDrug Resistance, NeoplasmDrug SynergismGene Expression Regulation, NeoplasticHormone AntagonistsHumansMaleMifepristoneProstatic NeoplasmsReceptors, GlucocorticoidTaxoidsTumor Cells, CulturedCyproterone AcetateDocetaxelHormone AntagonistsMifepristoneReceptors, GlucocorticoidTaxoidsdocetaxelglucocorticoid receptorprostate cancertherapy resistance

Identifiers

PMID26483423
PMCPMC4657186
OpenAlexW2178537302

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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.