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Research Article

Chemoprevention of preclinical breast and lung cancer with the bromodomain inhibitor I-BET 762

Di Zhang, Ana S. Leal, Sarah Carapellucci, Kayla Zydeck, Michael B. Sporn and Karen T. Liby
Di Zhang
Pharmacology and Toxicology, Michigan State University
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Ana S. Leal
Pharmacology and Toxicology, Michigan State University
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Sarah Carapellucci
Pharmacology and Toxicology, Michigan State University
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Kayla Zydeck
Pharmacology and Toxicology, Michigan State University
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Michael B. Sporn
Department of Pharmacology, Geisel School of Medicine at Dartmouth
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Karen T. Liby
Pharmacology and Toxicology, Michigan State University
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  • For correspondence: libykare@msu.edu
DOI: 10.1158/1940-6207.CAPR-17-0264
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Abstract

Breast cancer and lung cancer remain the top two leading causes of cancer death in women. Due to limited success in reducing the high mortality of these diseases, new drugs and approaches are desperately needed. Cancer prevention is one such promising strategy that is effective in both preclinical and clinical studies. I-BET 762 is a new bromodomain inhibitor that reversibly targets BET (bromodomain and extra-terminal) proteins and impairs their ability to bind to acetylated lysines on histones, thus interrupting downstream transcription. This inhibitor has anti-inflammatory effects and induces growth arrest in many cancers and is currently under clinical trials for treatment of cancer. However, few studies have investigated the chemopreventive effects of bromodomain inhibitors. Here, we found that I-BET 762 significantly delayed tumor development in preclinical breast and lung cancer mouse models. This drug not only induced growth arrest and downregulated c-Myc, pSTAT3 and pERK protein expression in tumor cells in vitro and in vivo but also altered immune populations in different organs. These results demonstrate the promising potential of using I-BET 762 for cancer prevention and suggest the striking effects of I-BET 762 are the result of targeting both tumor cells and the tumor microenvironment.

  • Received August 18, 2017.
  • Revision received October 23, 2017.
  • Accepted December 8, 2017.
  • Copyright ©2017, American Association for Cancer Research.
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Published OnlineFirst December 15, 2017
doi: 10.1158/1940-6207.CAPR-17-0264

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Chemoprevention of preclinical breast and lung cancer with the bromodomain inhibitor I-BET 762
Di Zhang, Ana S. Leal, Sarah Carapellucci, Kayla Zydeck, Michael B. Sporn and Karen T. Liby
Cancer Prev Res December 15 2017 DOI: 10.1158/1940-6207.CAPR-17-0264

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Chemoprevention of preclinical breast and lung cancer with the bromodomain inhibitor I-BET 762
Di Zhang, Ana S. Leal, Sarah Carapellucci, Kayla Zydeck, Michael B. Sporn and Karen T. Liby
Cancer Prev Res December 15 2017 DOI: 10.1158/1940-6207.CAPR-17-0264
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Cancer Prevention Research
eISSN: 1940-6215
ISSN: 1940-6207

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