Enhancer remodeling regulates epigenetic adaptation and resistance to MEK1/2 inhibition in triple-negative breast cancer. (2nd November 2017)

• Record Type: Journal Article
• Authors: Bevill, Samantha M.; Zawistowski, Jon S.; Johnson, Gary L.
• Is Part Of: Molecular & cellular oncology. Volume 4:Number 6(2017)
• Publication Date: 2017-11-02
• Subjects: Adaptive resistance -- BRD4 -- enhancer remodeling -- MEK inhibition -- P-TEFb complex; Tumors -- Periodicals; Neoplasms; Periodicals; 616.99
• DOI: 10.1080/23723556.2017.1300622
• Languages: English
• ISSNs: 2372-3556

Abstract

ABSTRACT: Kinase inhibitors targeting the mitogen/extracellular signal-regulated kinase kinase (MEK)- extracellular signal related kinase (ERK) signaling pathway have limited durability in inhibiting growth of triple-negative breast cancer. We defined genome wide enhancer remodeling following MEK inhibition capable of driving adaptive gene transcription. Targeting positive elongation factor (P-TEFb) transcriptional regulatory complex members can block enhancer remodeling making the response to MEK-ERK inhibition durable.