scholarly journals Inhibition of EZH2 by chemo- and radiotherapy agents and small molecule inhibitors induces cell death in castration-resistant prostate cancer

Oncotarget ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 3440-3452 ◽  
Author(s):  
Changping Wu ◽  
Xin Jin ◽  
Jing Yang ◽  
Yinhui Yang ◽  
Yundong He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

2016 ◽  
Vol 113 (26) ◽  
pp. 7124-7129 ◽  
Author(s):  
Kanak Raina ◽  
Jing Lu ◽  
Yimin Qian ◽  
Martha Altieri ◽  
Deborah Gordon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Xenograft Model ◽  
The United States ◽  
Castration Resistant Prostate Cancer ◽  
Secondary Resistance ◽  
Cellular Models ◽  
Castration Resistant ◽  
Mouse Xenograft Model ◽  
Bet Inhibitors

Prostate cancer has the second highest incidence among cancers in men worldwide and is the second leading cause of cancer deaths of men in the United States. Although androgen deprivation can initially lead to remission, the disease often progresses to castration-resistant prostate cancer (CRPC), which is still reliant on androgen receptor (AR) signaling and is associated with a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance invariably emerges, and new therapies are urgently needed. Recently, inhibitors of bromodomain and extra-terminal (BET) family proteins have shown growth-inhibitory activity in preclinical models of CRPC. Here, we demonstrate that ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. Unlike BET inhibitors, ARV-771 results in suppression of both AR signaling and AR levels and leads to tumor regression in a CRPC mouse xenograft model. This study is, to our knowledge, the first to demonstrate efficacy with a small-molecule BET degrader in a solid-tumor malignancy and potentially represents an important therapeutic advance in the treatment of CRPC.

scholarly journals Gambogic acid inhibits thioredoxin activity and induces ROS-mediated cell death in castration-resistant prostate cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 77181-77194 ◽  
Author(s):  
Hong Pan ◽  
Keith H. Jansson ◽  
Michael L. Beshiri ◽  
JuanJuan Yin ◽  
Lei Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Gambogic Acid ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
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