Abstract A011: Interplay of AR co-activators, CBP/p300, and immune regulation in prostate cancer

作者：Paula O. Cooper, Stefan DiFazio, Laila Scroggins, Raunak Shrestha, Leigh Ellis, Cara C. Schafer, Ayesha A. Shafi · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.prostateca26-a011 · 研究领域：Protein Degradation and Inhibitors、Prostate Cancer Treatment and Research、Advanced Breast Cancer Therapies

Abstract Prostate cancer (PCa) remains a significant health burden as the most diagnosed malignancy and the second leading cause of cancer death in U.S. men. Androgen receptor (AR) signaling drives PCa progression, yet the effects of androgen deprivation therapy are short-lived, and castration-resistant prostate cancer (CRPC) inevitably emerges. CBP/p300, transcriptional co-activators, play crucial roles in regulating AR, MYC, and other oncogenic drivers. Our preliminary data and ongoing clinical trial findings suggest that CBP/p300 inhibition compromises AR/MYC activity, reducing PCa cell growth in vitro and in vivo. In addition to their contributions to PCa progression, AR and MYC can also modulate immune regulatory factors; however, the role of CBP/p300 in modulating T cell-regulatory pathways and immune evasion mechanisms in PCa remains poorly defined. The purpose of this study is to evaluate how CBP/p300 activity in tumor cells modulates immune signaling and surface expression of T cell regulatory factors, with the goal of defining mechanisms of immune suppression driven by AR/MYC and CBP/p300 interplay. Ultimately, these findings may lead to better treatments that address immune dysregulation in the TME and inform therapeutic strategies integrating CBP/p300 inhibition with immunotherapy. We performed transcriptomic profiling of multiple PCa cell lines following CBP or p300 knockdown or cells treated with pharmacological inhibition using the clinical CBP/p300 bromodomain...