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|Title:||The androgen receptor is a tumor suppressor in estrogen receptor-positive breast cancer|
|Citation:||Nature Medicine, 2021; 27(2):310-320|
|Theresa E. Hickey, Luke A. Selth, Kee Ming Chia, Geraldine Laven-Law, Heloisa H. Milioli, Daniel Roden ... et al.|
|Abstract:||The role of the androgen receptor (AR) in estrogen receptor (ER)-α-positive breast cancer is controversial, constraining implementation of AR-directed therapies. Using a diverse, clinically relevant panel of cell-line and patient-derived models, we demonstrate that AR activation, not suppression, exerts potent antitumor activity in multiple disease contexts, including resistance to standard-of-care ER and CDK4/6 inhibitors. Notably, AR agonists combined with standard-of-care agents enhanced therapeutic responses. Mechanistically, agonist activation of AR altered the genomic distribution of ER and essential co-activators (p300, SRC-3), resulting in repression of ER-regulated cell cycle genes and upregulation of AR target genes, including known tumor suppressors. A gene signature of AR activity positively predicted disease survival in multiple clinical ER-positive breast cancer cohorts. These findings provide unambiguous evidence that AR has a tumor suppressor role in ER-positive breast cancer and support AR agonism as the optimal AR-directed treatment strategy, revealing a rational therapeutic opportunity.|
|Keywords:||Cell Line, Tumor|
Estrogen Receptor alpha
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
Nuclear Receptor Coactivator 3
|Rights:||© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.|
|Appears in Collections:||Aurora harvest 8|
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