| Literature DB >> 28819026 |
Lingyan Jin1, Jesse Garcia2, Emily Chan2, Cecile de la Cruz2, Ehud Segal2, Mark Merchant2, Samir Kharbanda3, Ryan Raisner1, Peter M Haverty4, Zora Modrusan5, Justin Ly6, Edna Choo6, Susan Kaufman7, Maureen H Beresini7, F Anthony Romero8, Steven Magnuson9, Karen E Gascoigne10.
Abstract
Resistance invariably develops to antiandrogen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here, we report that the transcriptional coactivator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression. Our findings offer a preclinical proof of concept for small-molecule therapies to target the CBP/p300 bromodomain as a strategy to treat castration-resistant prostate cancer. Cancer Res; 77(20); 5564-75. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
Mesh：
Substances：
Year: 2017 PMID： 28819026 DOI： 10.1158/0008-5472.CAN-17-0314
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701