Evidence map›Paper›PMID 33260953›Full record

ArticleCancers2020

Inhibition of Serum Response Factor Improves Response to Enzalutamide in Prostate Cancer.

R William Watson, Haleema Azam, Claudia Aura, Niamh Russell, Janet McCormack, Eva Corey, Colm Morrissey, John Crown, William M Gallagher, Maria Prencipe

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 29% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
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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

10 authors at 3 institutions in 2 countries.

R William WatsonConway Institute of Biomolecular and Biomedical Research, UCD School of Medicine, University College Dublin, Belfield, D4, Dublin, Ireland.ORCID 0000-0001-8831-3244
Haleema AzamCancer Biology and Therapeutics Laboratory, UCD Conway Institute, University College Dublin, Belfield, D4, Dublin, Ireland.
Claudia AuraCancer Biology and Therapeutics Laboratory, UCD Conway Institute, University College Dublin, Belfield, D4, Dublin, Ireland.
Niamh RussellCancer Biology and Therapeutics Laboratory, UCD Conway Institute, University College Dublin, Belfield, D4, Dublin, Ireland.ORCID 0000-0001-5003-8646
Janet McCormackResearch Pathology Core, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield D4, Dublin, Ireland.
Eva CoreyDepartment of Urology, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0002-9244-3807
Colm MorrisseyDepartment of Urology, University of Washington, Seattle, WA 98195, USA.
John CrownDepartment of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland.
William M GallagherCancer Biology and Therapeutics Laboratory, UCD Conway Institute, University College Dublin, Belfield, D4, Dublin, Ireland.ORCID 0000-0002-4307-5999
Maria PrencipeCancer Biology and Therapeutics Laboratory, UCD Conway Institute, University College Dublin, Belfield, D4, Dublin, Ireland.ORCID 0000-0002-8864-1560
University College Dublin · IEUniversity of Washington · USSt. Vincent's University Hospital · IE

Funding

Department of Defense Prostate Cancer Biorepository Network (PCBN) W81XWH-14-2-0183Irish Cancer Society #CRF12PREPacific Northwest Prostate Cancer SPORE P50CA97186PO1 NIH grant PO1 CA163227Science Foundation Ireland 18/SIRG/5510Science Foundation Ireland OPTi-PREDICT grant #15/IA/3104Science Foundation Ireland Strategic Research Programme Precision Oncology Ireland grant #18/SPP/3522
6 · The paper itself

Abstract

Castrate-resistant prostate cancer (CRPC) is challenging to treat with the androgen receptor (AR), the main target and key focus of resistance. Understanding the mechanisms of AR interaction with co-regulators will identify new therapeutic targets to overcome AR resistance mechanisms. We previously identified the serum response factor (SRF) as a lead target in an in vitro model of CRPC and showed that SRF expression in tissues of CRPC patients was associated with shorter survival. Here, we tested SRF inhibition in vitro and in vivo to assess SRF as a potential target in CRPC. Inhibition of SRF with the small-molecule inhibitor CCG1423 resulted in enhanced response to enzalutamide in vitro and reduced tumour volume of LuCaP 35CR, a CRPC patient-derived xenograft model. Nuclear localisation of AR post-CCG1423 was significantly decreased and was associated with decreased α-tubulin acetylation in vitro and decreased prostate specific antigen (PSA) levels in vivo. SRF immunoreactivity was tested in metastatic tissues from CRPC patients to investigate its role in enzalutamide response. Kaplan-Meier curves showed that high SRF expression was associated with shorter response to enzalutamide. Our study supports the use of SRF inhibitors to improve response to enzalutamide.

Indexed as

androgen receptorenzalutamideprostate cancerserum response factor

Identifiers

PMID33260953
PMCPMC7760758
OpenAlexW3109651038

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.