Chemoprevention of Preclinical Breast and Lung Cancer with the Bromodomain Inhibitor I-BET 762

Overview

Journal Cancer Prev Res (Phila)

Specialty Oncology

Date 2017 Dec 17

PMID 29246957

Citations 13

Authors

Di Zhang

Ana S Leal

Sarah Carapellucci

Kayla Zydeck

Michael B Sporn

Karen T Liby

Affiliations

Soon will be listed here.

Abstract

Breast cancer and lung cancer remain the top two leading causes of cancer-related deaths in women. Because of 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 extraterminal) 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 and 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. .

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