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TOP2A and EZH2 prov...
TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup
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- Labbé, David P. (author)
- Dana-Farber Cancer Institute,Harvard Medical School
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- Sweeney, Christopher J. (author)
- Harvard Medical School
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- Brown, Myles (author)
- Harvard Medical School,Dana-Farber Cancer Institute
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- Galbo, Phillip (author)
- Roswell Park Cancer Institute
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- Rosario, Spencer (author)
- Roswell Park Cancer Institute
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- Wadosky, Kristine M. (author)
- Roswell Park Cancer Institute
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- Ku, Sheng Yu (author)
- Roswell Park Cancer Institute
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- Sjöström, Martin (author)
- Lund 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
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- Alshalalfa, Mohammed (author)
- GenomeDx Biosciences
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- Erho, Nicholas (author)
- GenomeDx Biosciences
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- Davicioni, Elai (author)
- GenomeDx Biosciences
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- Karnes, R. Jeffrey (author)
- Mayo Clinic Minnesota
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- Schaeffer, Edward M. (author)
- Northwestern University
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- Jenkins, Robert B. (author)
- Mayo Clinic Minnesota
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- Den, Robert B. (author)
- Thomas Jefferson University
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Ross, Ashley E. (author)
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- Bowden, Michaela (author)
- Harvard Medical School
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- Huang, Ying (author)
- Harvard Medical School
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- Gray, Kathryn P. (author)
- Harvard University
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- Feng, Felix Y. (author)
- University of Texas Health Science Centre
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- Spratt, Daniel E. (author)
- University of Michigan
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- Goodrich, David W. (author)
- Roswell Park Cancer Institute
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- Eng, Kevin H. (author)
- Roswell Park Cancer Institute
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- Ellis, Leigh (author)
- Brigham and Women's Hospital / Harvard Medical School
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(creator_code:org_t)
- 2017
- 2017
- English 12 s.
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In: Clinical Cancer Research. - 1078-0432. ; 23:22, s. 7072-7083
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (subject category)
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- By the author/editor
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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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show more...
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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Clinical Cancer ...
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Lund University