Pd35-07 Identifying and Targeting Upregulated Histone Modifying Enzymes Involved in Prostate Cancer Cell Survival After Androgen Deprivation Therapy

You have accessJournal of UrologyProstate Cancer: Basic Research n=9). Candidate HME protein expression was examined in ADT-treated LNCaP cells by Western. A tissue microarray(TMA) was constructed from 32 ADT-treated and 29 untreated post-prostatectomy samples to evaluate EZH1 expression with immunohistochemistry. LNCaP cells were exposed to the EZH1/2 FDA-approved inhibitor Valemetostat± ADT and synergy was calculated (Calcusyn™). RESULTS: Compared to untreated tumors, ADT-treated samples upregulate 18 candidate HMEs in RNA-seq data. Analysis of ADT-treated samples in the public datasets validated the upregulation of four HMEs: EZH1, MECOM, HDAC5, and PRDM16 (p<0.1). EZH1, a histone methyltransferase within the PRC2 complex, increases in LNCaP cells up to 2 weeks after ADT exposure. Comparing ADT-treated and untreated PC tumors reveal a persistence of EZH1 expression at 3mo after ADT (24 % vs 26%, respectively). Combination therapy with Valemetostat± ADT did not demonstrate a synergistic effect in LNCaP cells . Days to PSA recurrence negatively correlated with EZH1 expression in the ADT-treated PC tumors(r=-0.22) suggesting that high expression of EZH1 might predict worse patient outcomes. CONCLUSIONS: We identified EZH1 as a HME with persistent/upregulated expression in PC after ADT treatment. EZH1 is a histone methyltransferase involved in preventing senescence that represents a potential enzyme target (when specifically, targeted) when combined with ADT to improve tumor responses. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e727 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Tanaya Purohit More articles by this author Emily Schmitt More articles by this author Marcelo Bigarella More articles by this author Kayla Bahr More articles by this author Sean Sardeson More articles by this author Diana Garcia More articles by this author Karla Esbona More articles by this author Peter W. Lewis More articles by this author John M. Denu More articles by this author Wei Huang More articles by this author Bing Yang More articles by this author David Jarrard More articles by this author Expand All Advertisement PDF downloadLoading ...