Evidence map›Paper›PMID 33799432›Full record

ArticleCancers2021

Molecular Profiling of Docetaxel-Resistant Prostate Cancer Cells Identifies Multiple Mechanisms of Therapeutic Resistance.

Thiago S Lima, Diego Iglesias-Gato, Luciano D O Souza, Jan Stenvang, Diego S Lima, Martin A Røder, Klaus Brasso, José M A Moreira

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.1field-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.

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

20 citing papers in PubMed, 37 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

8 authors at 3 institutions in 2 countries.

Thiago S LimaDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.ORCID 0000-0001-9680-7906
Diego Iglesias-GatoDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
Luciano D O SouzaDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.ORCID 0000-0003-4260-8615
Jan StenvangDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.ORCID 0000-0001-5647-4828
Diego S LimaDepartment of Cytogenetics, Albert Sabin Children's Hospital, Fortaleza 60410-794, Brazil.
Martin A RøderCopenhagen Prostate Cancer Center, Department of Urology, Copenhagen University Hospital, 2100 Copenhagen, Denmark.ORCID 0000-0002-0019-5333
Klaus BrassoCopenhagen Prostate Cancer Center, Department of Urology, Copenhagen University Hospital, 2100 Copenhagen, Denmark.ORCID 0000-0001-6562-6416
José M A MoreiraDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.ORCID 0000-0002-9944-1214
University of Copenhagen · DKCopenhagen University Hospital · DKHospital Infantil Albert Sabin · BR

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior BEX 13421/13-1Danish Cancer Society R90-A6109
6 · The paper itself

Abstract

Docetaxel-a taxane-based chemotherapeutic agent-was the first treatment to demonstrate significant improvements in overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, the response to docetaxel is generally short-lived, and relapse eventually occurs due to the development of resistance. To explore the mechanisms of acquired docetaxel resistance in prostate cancer (PCa) and set these in the context of androgen deprivation therapy, we established docetaxel-resistant PCa cell lines, derived from the androgen-dependent LNCaP cell line, and from the LNCaP lineage-derived androgen-independent C4-2B sub-line. We generated two docetaxel-resistant LNCaPR and C4-2BR sub-lines, with IC50 values 77- and 50-fold higher than those of the LNCaP and C4-2B parental cells, respectively. We performed gene expression analysis of the matched sub-lines and found several alterations that may confer docetaxel resistance. In addition to increased expression of ABCB1, an ATP-binding cassette (ABC) transporter, and a well-known gene associated with development of docetaxel resistance, we identified genes associated with androgen signaling, cell survival, and overexpression of ncRNAs. In conclusion, we identified multiple mechanisms that may be associated with the development of taxane drug resistance in PCa. Actioning these mechanisms could provide a potential approach to re-sensitization of docetaxel-resistant PCa cells to docetaxel treatment and thereby further add to the life-prolonging effects of this drug in men with mCRPC.

Indexed as

androgen independencecellular modelsdocetaxel resistanceprostate cancer

Identifiers

PMID33799432
PMCPMC7998254
OpenAlexW3138747339

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.