Accession Number:

AD1141237

Title:

Exploit Dimethyl Fumarate to Uncover Druggable Vulnerabilities and Prevent Recurrence of ER+ Breast Cancers

Descriptive Note:

[Technical Report, Annual Report]

Corporate Author:

Loyola University of Chicago

Personal Author(s):

Report Date:

2021-03-01

Pagination or Media Count:

10

Abstract:

ZNF217 transcription factor was identified as a target of dimethyl fumarate DMF in cell models of aggressive ER breast cancer. ZNF217 amplification is associated aggressive tumor features, resistance to endocrine therapy and poor outcome in breast cancer. This evidence indicates that inhibition of ZNF217 will be beneficial, however there are no know direct inhibitors of ZNF217. We show that DMF covalently modifies ZNF217 and inhibits its transcriptional activity. Furthermore, DMF inhibits ZNF217-driven phenotypes such as clonogenic survival and stemness. Cells with higher expression of ZNF217 are more sensitive to ZNF217 inhibition by DMF. Lastly, DMF treatment causes significant tumor regression in a xenograft model. These data suggest that DMF can be the prototype drug upon which to generate improved and more specific inhibitors for ZNF217. Overall, this data could be the basis for a new treatment strategy against aggressive breast cancer, especially to overcome resistance and recurrence.

Descriptors:

Subject Categories:

  • Medicine and Medical Research
  • Biochemistry

Distribution Statement:

[A, Approved For Public Release]