Exploit Dimethyl Fumarate to Uncover Druggable Vulnerabilities and Prevent Recurrence of ER+ Breast Cancers
Abstract
To define the effects of DMF in preventing recurrence in a xenograft models of ER+ breast cancers (Specific Aim 1), we established xenografts in mice and treated them with vehicle, DMF, Tamoxifen, or DMF+Tamoxifen for 4 weeks. Tumors were excised, RNA was isolated and RNA transcriptomic analysis was conducted. Among the top pathways regulated by both DMF+Tamoxifenwere related to immune, host defense response and interferon signaling. We conducted simultaneously chemoproteomics to identify global succination targets of DMF in this setting (Specific Aim 2) and among those targets, covalent modification of IRF9 is currently being investigated for its relevance to interferon signaling and its impact on tumor recurrence. In summary, two complementary approaches, RNA transcriptomic analysis and chemoproteomics, are converging on identifying the IRF9/interferon signaling as critical to tumor recurrence and a therapeutic target of DMF in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2022
- Accession Number
- AD1177764
Entities
People
- Irida Kastrati
Organizations
- Loyola University New Orleans