Targeting FOXA1-Mediated Epigenetic Reprogramming in Aggressive Salivary Gland Cancer
Abstract
Salivary duct carcinoma (SDC) is a rare, aggressive type of salivary gland cancer that has high expression of androgen receptor (AR) and AR-regulated genes. FOXA1 is a nuclear protein required for AR-regulated gene expression and tumor growth/survival. FOXA1 expression is also strongly correlated with AR expression in SDC, and subsets of these tumors harbor FOXA1 gene alterations that have previously been shown to enhance AR-regulated gene expression in prostate cancer. Taken together, these data implicate FOXA1 as a critical regulator of AR signaling in SDC; however, FOXA1 itself is not directly targetable. Intriguingly, the nuclear protein LSD1 regulates FOXA1 activity in prostate cancer, and the LSD1 inhibitor GSK2879552 has been shown to disrupt FOXA1-dependent AR signaling and tumor growth/survival. Thus, the goal of this proposed research is to characterize the FOXA1 cistrome in salivary duct carcinoma and determine the efficacy of the LSD1 inhibitor GSK2879552 for disrupting FOXA1-mediated epigenetic reprogramming and tumor growth in ex vivo organoid cultures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1190801
Entities
People
- Aaron M. Udager
Organizations
- Board of Regents of the University of Michigan