Evidence map›Paper›PMID 35965411›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023

DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer.

Thi Khanh Le, Chaïma Cherif, Kenneth Omabe, Clément Paris, François Lannes, Stéphane Audebert, Emilie Baudelet, Mourad Hamimed, Dominique Barbolosi, Pascal Finetti and 6 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 3 countries.

Thi Khanh LePredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France; Department of Life Science, University of Science and Technology of Hanoi, Hanoi 000084, Vietnam.
Chaïma CherifPredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France.
Kenneth OmabePredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France.
Clément ParisPredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France.
François LannesPredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France; Urology Deparment, AP-HM Hospital Nord, Aix-Marseille University, 13915 Marseille Cedex 20, France.
Stéphane AudebertMarseille Protéomique, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Institut Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, France.
Emilie BaudeletMarseille Protéomique, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Institut Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, France.
Mourad HamimedInria - Inserm team COMPO, COMPutational pharmacology and clinical Oncology, Centre Inria Sophia Antipolis - Méditerranée, Centre de Recherches en Cancérologie de Marseille, Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Boulevard Jean Moulin, 13005 Marseille, France.
Dominique BarbolosiInria - Inserm team COMPO, COMPutational pharmacology and clinical Oncology, Centre Inria Sophia Antipolis - Méditerranée, Centre de Recherches en Cancérologie de Marseille, Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Boulevard Jean Moulin, 13005 Marseille, France.
Pascal FinettiPredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France.
Cyrille BastideUrology Deparment, AP-HM Hospital Nord, Aix-Marseille University, 13915 Marseille Cedex 20, France.
Ladan FazliThe Vancouver Prostate Centre, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
Martin GleaveThe Vancouver Prostate Centre, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
François BertucciPredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France.
David TaïebPredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France; La Timone University Hospital, Aix-Marseille University, 13005 Marseille, France; European Center for Research in Medical Imaging, Aix-Marseille University, 13005 Marseille, France.
Palma RocchiPredictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, 13273 Marseille, France; European Center for Research in Medical Imaging, Aix-Marseille University, 13005 Marseille, France. Electronic address: palma.rocchi@inserm.fr.
Centre National de la Recherche Scientifique · FRUniversity of British Columbia · CAAix-Marseille Université · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The heat shock protein 27 (Hsp27) has emerged as a principal factor of the castration-resistant prostate cancer (CRPC) progression. Also, an antisense oligonucleotide (ASO) against Hsp27 (OGX-427 or apatorsen) has been assessed in different clinical trials. Here, we illustrate that Hsp27 highly regulates the expression of the human DEAD-box protein 5 (DDX5), and we define DDX5 as a novel therapeutic target for CRPC treatment. DDX5 overexpression is strongly correlated with aggressive tumor features, notably with CRPC. DDX5 downregulation using a specific ASO-based inhibitor that acts on DDX5 mRNAs inhibits cell proliferation in preclinical models, and it particularly restores the treatment sensitivity of CRPC. Interestingly, through the identification and analysis of DDX5 protein interaction networks, we have identified some specific functions of DDX5 in CRPC that could contribute actively to tumor progression and therapeutic resistance. We first present the interactions of DDX5 and the Ku70/80 heterodimer and the transcription factor IIH, thereby uncovering DDX5 roles in different DNA repair pathways. Collectively, our study highlights critical functions of DDX5 contributing to CRPC progression and provides preclinical proof of concept that a combination of ASO-directed DDX5 inhibition with a DNA damage-inducing therapy can serve as a highly potential novel strategy to treat CRPC.

Indexed as

Oligonucleotides, AntisenseProstatic Neoplasms, Castration-ResistantCell Line, TumorDEAD-box RNA HelicasesHSP27 Heat-Shock ProteinsHumansMaleRNA, MessengerDdx5 protein, humanDEAD-box RNA HelicasesHSP27 Heat-Shock ProteinsOligonucleotides, AntisenseRNA, Messengerantisense oligonucleotides (ASOs)castration-resistant prostate cancer (CRPC)DDX5DNA damage response (DDR)Hsp27protein interactionstherapeutic ressistance

Identifiers

PMID35965411
PMCPMC9931527
OpenAlexW4291222812

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.