Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer

Shaokun Shu, Charles Y. Lin, Housheng Hansen He, Robert M. Witwicki, Doris P. Tabassum, Justin M. Roberts, Michalina Janiszewska, Sung Jin Huh, Yi Liang, Jeremy Ryan, Ernest Doherty, Hisham Mohammed, Hao Guo, Daniel G. Stover, Muhammad B. Ekram, Guillermo Peluffo, Jonathan Brown, Clive D’Santos, Ian E. Krop, Deborah Dillon, Michael McKeown, Christopher Ott, Jun Qi, Min Ni, Prakash K. Rao, Melissa Duarte, Shwu-Yuan Wu, Cheng-Ming Chiang, Lars Anders, Richard A. Young, Eric P. Winer, Antony Letai, William T. Barry, Jason S. Carroll, Henry W. Long, Myles Brown, X. Shirley Liu, Clifford A. Meyer, James E. Bradner () and Kornelia Polyak ()
Additional contact information
Shaokun Shu: Dana-Farber Cancer Institute
Charles Y. Lin: Dana-Farber Cancer Institute
Housheng Hansen He: Dana-Farber Cancer Institute
Robert M. Witwicki: Dana-Farber Cancer Institute
Doris P. Tabassum: Dana-Farber Cancer Institute
Justin M. Roberts: Dana-Farber Cancer Institute
Michalina Janiszewska: Dana-Farber Cancer Institute
Sung Jin Huh: Dana-Farber Cancer Institute
Yi Liang: Princess Margaret Cancer Center/University Health Network
Jeremy Ryan: Dana-Farber Cancer Institute
Ernest Doherty: Dana-Farber Cancer Institute
Hisham Mohammed: Cancer Research UK, Cambridge Institute, University of Cambridge
Hao Guo: Dana-Farber Cancer Institute, Harvard School of Public Health
Daniel G. Stover: Dana-Farber Cancer Institute
Muhammad B. Ekram: Dana-Farber Cancer Institute
Guillermo Peluffo: Dana-Farber Cancer Institute
Jonathan Brown: Dana-Farber Cancer Institute
Clive D’Santos: Cancer Research UK, Cambridge Institute, University of Cambridge
Ian E. Krop: Dana-Farber Cancer Institute
Deborah Dillon: Dana-Farber Cancer Institute
Michael McKeown: Dana-Farber Cancer Institute
Christopher Ott: Dana-Farber Cancer Institute
Jun Qi: Dana-Farber Cancer Institute
Min Ni: Dana-Farber Cancer Institute
Prakash K. Rao: Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute
Melissa Duarte: Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute
Shwu-Yuan Wu: Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center
Cheng-Ming Chiang: Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center
Lars Anders: Whitehead Institute for Biomedical Research
Richard A. Young: Whitehead Institute for Biomedical Research
Eric P. Winer: Dana-Farber Cancer Institute
Antony Letai: Dana-Farber Cancer Institute
William T. Barry: Brigham and Women’s Hospital, Harvard Medical School
Jason S. Carroll: Cancer Research UK, Cambridge Institute, University of Cambridge
Henry W. Long: Dana-Farber Cancer Institute
Myles Brown: Dana-Farber Cancer Institute
X. Shirley Liu: Dana-Farber Cancer Institute, Harvard School of Public Health
Clifford A. Meyer: Dana-Farber Cancer Institute, Harvard School of Public Health
James E. Bradner: Dana-Farber Cancer Institute
Kornelia Polyak: Dana-Farber Cancer Institute

Nature, 2016, vol. 529, issue 7586, 413-417

Abstract: BET inhibitors that target bromodomain chromatin readers such as BRD4 are being explored as potential therapeutics in cancer; here triple-negative breast cancer cell lines are shown to respond to BET inhibitors and resistance seems to be associated with transcriptional changes rather than drug efflux and mutations, opening potential avenues to improve clinical responses to BET inhibitors.

Date: 2016
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DOI: 10.1038/nature16508

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