Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade Journal Article


Authors: Arora, V. K.; Schenkein, E.; Murali, R.; Subudhi, S. K.; Wongvipat, J.; Balbas, M. D.; Shah, N.; Cai, L.; Efstathiou, E.; Logothetis, C.; Zheng, D.; Sawyers, C. L.
Article Title: Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade
Abstract: The treatment of advanced prostate cancer has been transformed by novel antiandrogen therapies such as enzalutamide. Here, we identify induction of glucocorticoid receptor (GR) expression as a common feature of drug-resistant tumors in a credentialed preclinical model, a finding also confirmed in patient samples. GR substituted for the androgen receptor (AR) to activate a similar but distinguishable set of target genes and was necessary for maintenance of the resistant phenotype. The GR agonist dexamethasone was sufficient to confer enzalutamide resistance, whereas a GR antagonist restored sensitivity. Acute AR inhibition resulted in GR upregulation in a subset of prostate cancer cells due to relief of AR-mediated feedback repression of GR expression. These findings establish a mechanism of escape from AR blockade through expansion of cells primed to drive AR target genes via an alternative nuclear receptor upon drug exposure. © 2013 Elsevier Inc.
Journal Title: Cell
Volume: 155
Issue: 6
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2013-12-05
Start Page: 1309
End Page: 1322
Language: English
DOI: 10.1016/j.cell.2013.11.012
PROVIDER: scopus
PMCID: PMC3932525
PUBMED: 24315100
DOI/URL:
Notes: Export Date: 2 January 2014 -- CODEN: CELLB -- Source: Scopus
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MSK Authors
  1. Charles L Sawyers
    153 Sawyers
  2. Vivek Kumar Arora
    10 Arora
  3. Sumit Kumar Subudhi
    10 Subudhi
  4. Rajmohan Murali
    155 Murali
  5. Ling Cai
    3 Cai
  6. Neel Shah
    7 Shah
  7. Minna Delarae Balbas
    7 Balbas