Show simple item record

Files in this item


Item metadata

dc.contributor.authorAsim, Mohammad
dc.contributor.authorTarish, Firas
dc.contributor.authorZecchini, Heather I
dc.contributor.authorSanjiv, Kumar
dc.contributor.authorGelali, Eleni
dc.contributor.authorMassie, Charles E
dc.contributor.authorBaridi, Ajoeb
dc.contributor.authorWarren, Anne Y
dc.contributor.authorZhao, Wanfeng
dc.contributor.authorOgris, Christoph
dc.contributor.authorMcDuffus, Leigh-Anne
dc.contributor.authorMascalchi, Patrice
dc.contributor.authorShaw, Greg
dc.contributor.authorDev, Harveer
dc.contributor.authorWadhwa, Karan
dc.contributor.authorWijnhoven, Paul
dc.contributor.authorForment, Josep V
dc.contributor.authorLyons, Scott R
dc.contributor.authorLynch, Andy G
dc.contributor.authorO'Neill, Cormac
dc.contributor.authorZecchini, Vincent R
dc.contributor.authorRennie, Paul S
dc.contributor.authorBaniahmad, Aria
dc.contributor.authorTavaré, Simon
dc.contributor.authorMills, Ian G
dc.contributor.authorGalanty, Yaron
dc.contributor.authorCrosetto, Nicola
dc.contributor.authorSchultz, Niklas
dc.contributor.authorNeal, David
dc.contributor.authorHelleday, Thomas
dc.identifier.citationAsim , M , Tarish , F , Zecchini , H I , Sanjiv , K , Gelali , E , Massie , C E , Baridi , A , Warren , A Y , Zhao , W , Ogris , C , McDuffus , L-A , Mascalchi , P , Shaw , G , Dev , H , Wadhwa , K , Wijnhoven , P , Forment , J V , Lyons , S R , Lynch , A G , O'Neill , C , Zecchini , V R , Rennie , P S , Baniahmad , A , Tavaré , S , Mills , I G , Galanty , Y , Crosetto , N , Schultz , N , Neal , D & Helleday , T 2017 , ' Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer ' , Nature Communications , vol. 8 , 374 .
dc.identifier.otherPURE: 251034661
dc.identifier.otherPURE UUID: 27d0d84b-1d7b-47ce-8588-81368adb246e
dc.identifier.otherPubMed: 28851861
dc.identifier.otherPubMedCentral: PMC5575038
dc.identifier.otherScopus: 85028448581
dc.identifier.otherORCID: /0000-0002-7876-7338/work/36661765
dc.descriptionThis study was supported by the National Cancer Research Institute (National Institute of Health Research (NIHR) Collaborative Study: ‘Prostate Cancer: Mechanisms of Progression and Treatment (PROMPT)” (grant G0500966/75466). This work was funded by a Cancer Research UK program grant (D.N.), the Swedish Research Council (T.H.), AFA insurance (T.H.), Swedish Cancer Society (T.H.), the Swedish Pain Relief Foundation (T.H.), the Torsten and Ragnar Söderberg Foundation (T.H.), AstraZeneca (T.H.) Centre for Clinical Research (CKF) (F.T.), the Västmanland Research Foundation for Cancer in Vasteras (F.T.), the Henning and Ida Persson Research Foundation (F.T.).en
dc.description.abstractEmerging 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.
dc.relation.ispartofNature Communicationsen
dc.rights© 2017 The Authors. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleSynthetic lethality between androgen receptor signalling and the PARP pathway in prostate canceren
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Statisticsen
dc.contributor.institutionUniversity of St Andrews. Population and Behavioural Science Divisionen
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.description.statusPeer revieweden

This item appears in the following Collection(s)

Show simple item record