Toppling the HAT to Treat Lethal Prostate Cancer
Reyaz ur Rasool, Ramakrishnan Natesan, Irfan A. Asangani
Abstract
Abstract Summary: In this issue of Cancer Discovery, Welti and colleagues demonstrate a positive correlation between the expression of the histone acetyltransferase paralogs CBP and p300 with increased androgen receptor (AR) signaling and androgen deprivation therapy resistance in advanced prostate cancer. CCS1477, a selective inhibitor of p300/CBP bromodomain, disrupts AR- and MYC-regulated gene expression, suppresses tumor growth in vivo in multiple castration-resistant prostate cancer xenograft models, and modulates biomarker expression in early clinical evaluation, providing a novel therapeutic approach for AR-addicted advanced prostate cancer. See related article by Welti et al., p. 1118.