The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Glucocorticoid Receptor Confers Resistance to Antiandrogens by Bypassing Androgen Receptor Blockade
Open accessAbstract
Summary 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 novel mechanism of escape from AR blockade through expansion of cells primed to drive AR target genes via an alternative nuclear receptor upon drug exposure.
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Cites
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Cited by
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Metadata
- 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.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 155
- Issue
- 6
- Pages
- 1309-1322
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2080748037
- Cited by
- 986
- References
- 15
- FWCI
- 57.49
- Type
- journal article
- Language
- en
- Open access
- bronze
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- 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. (2013). Glucocorticoid Receptor Confers Resistance to Antiandrogens by Bypassing Androgen Receptor Blockade. Cell. https://doi.org/10.1016/j.cell.2013.11.012
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