Abstract 1518: Mechanisms of bromodomain and extra-terminal motif inhibitor (BETi) sensitivity in triple-negative breast cancer (TNBC)

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.1518-1518
• Main Authors: Schafer, Johanna, Lehmann, Brian, Liu, Phillip, Stubbs, Matthew, Scherle, Peggy, Pietenpol, Jennifer
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-1518

Triple-negative breast cancers (TNBCs) lack expression of estrogen receptor (ER), progesterone receptor (PR), and amplifications in the human epidermal growth factor receptor 2 (HER2). With currently no FDA-approved targeted therapies for TNBC, patients with TNBC have a higher risk of local and distant recurrence, and an overall increased rate of mortality. Recent studies have demonstrated increased sensitivity of TNBC to the anti-proliferative effects of BETi compared to the other breast cancer subtypes. To determine mechanisms of sensitivity to BET inhibition, we analyzed the effect of two BET inhibitors, INCB054329 and OTX-015, across a panel of TNBC cell line models and identified cell lines that were both sensitive and insensitive to BETi. With the intent of identifying biomarkers of sensitivity, we performed RNA-seq and precision nuclear run-on and sequencing (PRO-seq) on both sensitive and resistant cell line models and data generated identified significant differences in key growth regulatory and apoptotic signaling pathways, including notable differences in Myc-dependent signaling. Our data suggest potential biomarkers of BETi sensitivity that may be of value in further pre-clinical studies. Further, our results provide mechanistic rationale for combinations of BETi with select, targeted therapies in a disease that is in need of new therapeutic intervention. Citation Format: Johanna Schafer, Brian Lehmann, Phillip Liu, Matthew Stubbs, Peggy Scherle, Jennifer Pietenpol. Mechanisms of bromodomain and extra-terminal motif inhibitor (BETi) sensitivity in triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1518. doi:10.1158/1538-7445.AM2017-1518