Targeting histone abnormality in triple negative breast cancer
Technical Report,01 Aug 2016,31 Jul 2017
University of Pittsburgh Pittsburgh United States
Pagination or Media Count:
During this funding period, Dr. Nancy E. Davidson moved to University of Washington at Seattle and transferred the Partnering PI toDr. Steffi Oesterreich at University of Pittsburgh. Dr. Oesterreich worked closely together with initiating PI, Dr. Yi Huang, to decipher how histone abnormality contributes to TNBC tumorigenesis and explore how to apply novel epigenetic agents in the most favorable combination strategy against TNBC. In the prior funding period, the joint team has revealed coordinated overexpression of HDAC5 and LSD1 proteins in clinical breast tumor specimens and identified that sulforaphane SFN, a natural bioactive HDAC inhibitor, was able to destabilize LSD1 protein through down regulation ofHDAC5 expression. Combined use of SFN with a potent LSD1 inhibitor HCI-2509 significantly enhanced antineoplastic efficacy of SFN in MDA-MB-231xenografts in mice.
- Medicine and Medical Research