Enhancer remodeling regulates epigenetic adaptation and resistance to MEK1/2 inhibition in triple-negative breast cancer
- Resource Type
- article
- Authors
- Samantha M. Bevill; Jon S. Zawistowski; Gary L. Johnson
- Source
- Molecular & Cellular Oncology, Vol 4, Iss 6 (2017)
- Subject
- adaptive resistance
brd4
enhancer remodeling
mek inhibition
p-tefb complex
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
- Language
- English
- ISSN
- 2372-3556
23723556
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.