Evidence map›Paper›PMID 37270558›Full record

ArticleScientific reports2023

Investigation of enzalutamide, docetaxel, and cabazitaxel resistance in the castration resistant prostate cancer cell line C4 using genome-wide CRISPR/Cas9 screening.

Jakob Haldrup, Simone Weiss, Linnéa Schmidt, Karina Dalsgaard Sørensen

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
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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

4 authors at 2 institutions in 1 country.

Jakob Haldrup *Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Simone Weiss *Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Linnéa SchmidtDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Karina Dalsgaard SørensenDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. kdso@clin.au.dk.
Aarhus University Hospital · DKAarhus University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enzalutamide, docetaxel, and cabazitaxel treatment resistance is a major problem in metastatic castration resistant prostate cancer (mCRPC), but the underlying genetic determinants are poorly understood. To identify genes that modulate treatment response to these drugs, we performed three genome-wide CRISPR/Cas9 knockout screens in the mCRPC cell line C4. The screens identified seven candidates for enzalutamide (BCL2L13, CEP135, E2F4, IP6K2, KDM6A, SMS, and XPO4), four candidates for docetaxel (DRG1, LMO7, NCOA2, and ZNF268), and nine candidates for cabazitaxel (ARHGAP11B, DRG1, FKBP5, FRYL, PRKAB1, RP2, SMPD2, TCEA2, and ZNF585B). We generated single-gene C4 knockout clones/populations for all genes and could validate effect on treatment response for five genes (IP6K2, XPO4, DRG1, PRKAB1, and RP2). Altered enzalutamide response upon IP6K2 and XPO4 knockout was associated with deregulation of AR, mTORC1, and E2F signaling, and deregulated p53 signaling (IP6K2 only) in C4 mCRPC cells. Our study highlights the necessity of performing individual validation of candidate hits from genome-wide CRISPR screens. Further studies are needed to assess the generalizability and translational potential of these findings.

Indexed as

Prostatic Neoplasms, Castration-ResistantAntineoplastic Combined Chemotherapy ProtocolsBenzamidesCell LineCRISPR-Cas SystemsDocetaxelEarly Detection of CancerGTPase-Activating ProteinsHumansMaleNitrilesPhenylthiohydantoinTaxoidsTreatment OutcomeARHGAP11B protein, humanBenzamidescabazitaxelDocetaxelenzalutamideGTPase-Activating ProteinsNitrilesPhenylthiohydantoinTaxoids

Identifiers

PMID37270558
PMCPMC10239467
OpenAlexW4379260626

What OpenQuestion holds

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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.