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TOP2A and EZH2 prov...
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Labbé, David P.Dana-Farber Cancer Institute,Harvard Medical School
(författare)
TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup
- Artikel/kapitelEngelska2017
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:3a8494d8-96e9-4a9f-be88-d76b936f7281
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https://lup.lub.lu.se/record/3a8494d8-96e9-4a9f-be88-d76b936f7281URI
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https://doi.org/10.1158/1078-0432.CCR-17-0413DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Sweeney, Christopher J.Harvard Medical School
(författare)
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Brown, MylesHarvard Medical School,Dana-Farber Cancer Institute
(författare)
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Galbo, PhillipRoswell Park Cancer Institute
(författare)
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Rosario, SpencerRoswell Park Cancer Institute
(författare)
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Wadosky, Kristine M.Roswell Park Cancer Institute
(författare)
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Ku, Sheng YuRoswell Park Cancer Institute
(författare)
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Sjöström, MartinLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-msm
(författare)
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Alshalalfa, MohammedGenomeDx Biosciences
(författare)
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Erho, NicholasGenomeDx Biosciences
(författare)
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Davicioni, ElaiGenomeDx Biosciences
(författare)
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Karnes, R. JeffreyMayo Clinic Minnesota
(författare)
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Schaeffer, Edward M.Northwestern University
(författare)
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Jenkins, Robert B.Mayo Clinic Minnesota
(författare)
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Den, Robert B.Thomas Jefferson University
(författare)
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Ross, Ashley E.
(författare)
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Bowden, MichaelaHarvard Medical School
(författare)
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Huang, YingHarvard Medical School
(författare)
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Gray, Kathryn P.Harvard University
(författare)
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Feng, Felix Y.University of Texas Health Science Centre
(författare)
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Spratt, Daniel E.University of Michigan
(författare)
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Goodrich, David W.Roswell Park Cancer Institute
(författare)
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Eng, Kevin H.Roswell Park Cancer Institute
(författare)
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Ellis, LeighBrigham and Women's Hospital / Harvard Medical School
(författare)
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Dana-Farber Cancer InstituteHarvard Medical School
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Clinical Cancer Research23:22, s. 7072-70831078-0432
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Till lärosätets databas
- Av författaren/redakt...
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Labbé, David P.
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Sweeney, Christo ...
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Brown, Myles
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Galbo, Phillip
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Rosario, Spencer
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Wadosky, Kristin ...
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visa fler...
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Ku, Sheng Yu
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Sjöström, Martin
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Alshalalfa, Moha ...
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Erho, Nicholas
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Davicioni, Elai
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Karnes, R. Jeffr ...
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Schaeffer, Edwar ...
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Jenkins, Robert ...
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Den, Robert B.
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Ross, Ashley E.
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Bowden, Michaela
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Huang, Ying
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Gray, Kathryn P.
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Feng, Felix Y.
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Spratt, Daniel E ...
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Goodrich, David ...
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Eng, Kevin H.
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Ellis, Leigh
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- MEDICIN OCH HÄLSOVETENSKAP
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och Klinisk medicin
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och Cancer och onkol ...
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Clinical Cancer ...
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Lunds universitet