ResearchIn-Press PreviewCell biologyOncology
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10.1172/jci.insight.207543
Combined BET bromodomain and DNMT inhibition targets critical survival pathways in transdifferentiated prostate cancer
William K. Storck,1 Diana Flores,1 Anbarasu Kumaraswamy,1 Zhi Duan,2 Shrabastee Chakraborty,1 Chao Zhang,1 Eva Rodansky,1 Dhruv Khokhani,1 Olivia A. Swaim,1 Karan Bedi,3 Raymond G. Cavalcante,4 Canping Chen,5 Faming Zhao,5 Ya-Mei Hu,5 Zheng Xia,5 Ryan J. Rebernick,6 Marcin Cieslik,3 Rahul Mannan,6 Somnath Mahapatra,6 Arul M. Chinnaiyan,3 Aaron M. Udager,6 Joshua A. Kuleape,1 Catherine R. Alumkal,1 Hannah N. Beck,1 Peter S. Nelson,7 Colm Morrissey,7 Michael C. Haffner,8 Leigh Ellis,9 Yuzhuo Wang,10 Joel A. Yates,1 and Joshi J. Alumkal11
1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America
2Department of Internal Medicine, University of Michgan, Ann Arbor, United States of America
3Rogel Cancer Center, University of Michigan, Ann Arbor, United States of America
4Bioinformatics Core, University of Michigan, Ann Arbor, United States of America
5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
11Department of Internal Medicine, University of Michiagn, Ann Arbor, United States of America
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1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America
2Department of Internal Medicine, University of Michgan, Ann Arbor, United States of America
3Rogel Cancer Center, University of Michigan, Ann Arbor, United States of America
4Bioinformatics Core, University of Michigan, Ann Arbor, United States of America
5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
11Department of Internal Medicine, University of Michiagn, Ann Arbor, United States of America
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4Bioinformatics Core, University of Michigan, Ann Arbor, United States of America
5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
11Department of Internal Medicine, University of Michiagn, Ann Arbor, United States of America
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5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
11Department of Internal Medicine, University of Michiagn, Ann Arbor, United States of America
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5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
11Department of Internal Medicine, University of Michiagn, Ann Arbor, United States of America
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7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
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6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
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5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
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8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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4Bioinformatics Core, University of Michigan, Ann Arbor, United States of America
5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
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4Bioinformatics Core, University of Michigan, Ann Arbor, United States of America
5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
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6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
10Vancouver Prostate Centre, Vancouver, Canada
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5Department of Biomedical Engineering, Oregon Health & Science University, Portland, United States of America
6Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, United States of America
7Department of Urology, University of Washington, Seattle, United States of America
8Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, United States of America
9Center for Prostate Disease Research, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, United States of America
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Published August 11, 2026 - More info
Copyright © 2026, Storck et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
