Evidence map›Paper›PMID 28851861›Full record

ArticleNature communications2017

Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer.

Mohammad Asim, Firas Tarish, Heather I Zecchini, Kumar Sanjiv, Eleni Gelali, Charles E Massie, Ajoeb Baridi, Anne Y Warren, Wanfeng Zhao, Christoph Ogris and 20 more

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

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06168487 (Phase I Non-Randomized, Unblinded, Single-Center Trial of Oral Telmisartan Alone or Combined With Selected Standard of Care Therapies for Prostate Cancer), which is not on this map. Cited by 169 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed, 11 pooled it
7.3field-weighted citation impact, top 2% 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.

NCT06168487 phase1recruitingnot on this mapstarted 2024, after this paper: background citation

Phase I Non-Randomized, Unblinded, Single-Center Trial of Oral Telmisartan Alone or Combined With Selected Standard of Care Therapies for Prostate Cancer

TypeinterventionalSponsorTyler J CurielRan2024 to 2027Enrolled36ConditionsProstate CancerArmsTelmisartan, Standard of Care Regimen
3 · Its place in the literature

Who cites it

169 citing papers in PubMed, 11 syntheses or guidelines pooled it, 273 citations in OpenAlex.

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  16. Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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109 more citing papers are in PubMed but not listed here.

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

30 authors at 6 institutions in 5 countries.

Mohammad AsimCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK. mohammad.asim@cruk.cam.ac.uk.ORCID http://orcid.org/0000-0002-2074-5929
Firas TarishScience for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden.
Heather I ZecchiniCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Kumar SanjivScience for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden.
Eleni GelaliScience for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden.
Charles E MassieCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.ORCID http://orcid.org/0000-0003-2314-4843
Ajoeb BaridiCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Anne Y WarrenDepartment of Pathology, Addenbrooke's Cambridge University Hospital, Cambridge, CB2 0QQ, UK.
Wanfeng ZhaoDepartment of Pathology, Addenbrooke's Cambridge University Hospital, Cambridge, CB2 0QQ, UK.
Christoph OgrisScience for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden.
Leigh-Anne McDuffusCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Patrice MascalchiCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Greg ShawCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Harveer DevCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Karan WadhwaCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Paul WijnhovenThe Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK.
Josep V FormentThe Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK.
Scott R LyonsCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Andy G LynchCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Cormac O'NeillCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Vincent R ZecchiniCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Paul S RennieThe Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada, V6H 3Z6.
Aria BaniahmadInstitute of Human Genetics, Jena University Hospital, 07743, Jena, Germany.
Simon TavaréCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Ian G MillsCentre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, University of Oslo, 0318, Oslo, Norway.
Yaron GalantyThe Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK.
Nicola CrosettoScience for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden.
Niklas SchultzScience for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden.
David NealCancer Research UK Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK. david.neal@nds.ox.ac.uk.ORCID http://orcid.org/0000-0002-6033-5086
Thomas HelledayScience for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden. Thomas.helleday@scilifelab.se.
University of Cambridge · GBScience for Life Laboratory · SECancer Research UK · GBJena University Hospital · DEUniversity of British Columbia · CAUniversity of Oslo · NO

Funding

Cancer Research UK 18796Cancer Research UK 20406Medical Research Council G0500966Wellcome Trust 206388/Z/17/Z
6 · The paper itself

Abstract

Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo. Our data suggest that ADT can functionally impair HR prior to the development of castration resistance and that, this potentially could be exploited therapeutically using PARP inhibitors in combination with androgen-deprivation therapy upfront in advanced or high-risk prostate cancer.Tumours with homologous recombination (HR) defects become sensitive to PARPi. Here, the authors show that androgen receptor (AR) regulates HR and AR inhibition activates the PARP pathway in vivo, thus inhibition of both AR and PARP is required for effective treatment of high risk prostate cancer.

Indexed as

Synthetic Lethal MutationsCollagen Type XIHomologous RecombinationHumansMaleProstatic Neoplasms, Castration-ResistantReceptors, AndrogenSignal TransductionCollagen Type XIPARP protein, Bos taurusReceptors, Androgen

Identifiers

PMID28851861
PMCPMC5575038
OpenAlexW2625362849

What OpenQuestion holds

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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.