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Updated: Apr 27, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Reappraisal of glucocorticoids in castrate-resistant prostate cancer
Oliver Sartor1, Christopher C Parker, Johann de Bono
1Department of Urology and Medicine, Tulane Medical School, Tulane, New Orleans, Louisiana, USA.
Abstract:
Recent reports and discussions of preclinical prostate cancer models have emphasized the possibility that enzalutamide resistance may be mediated by glucocorticoid receptors (GR). In both in vitroand xenograft animal studies, it is possible to show that the GR is up-regulated in prostate cancer cell lines and that dexamethasone reverses enzalutamide induced growth inhibition. In these model systems, GR agonists can induce a subset of androgen receptor target genes including prostate-specific antigen. These investigators also report a correlation between GR expression in patient-derived prostate cancer specimens and clinical response to enzalutamide. The authors discuss the possibility that these findings have important clinical relevance. We note that the current clinical evidence for GR mediating drug resistance or disease progression in patients with castrate-resistant prostate cancer (CRPC) is very limited at best.
Insights
Glucocorticoid receptors (GR) may drive enzalutamide resistance in prostate cancer. Preclinical studies show GR activation reverses enzalutamide
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Enzalutamide is a key treatment for castration-resistant prostate cancer (CRPC).
- Emerging evidence suggests glucocorticoid receptors (GR) may play a role in enzalutamide resistance.
- Preclinical models provide a basis for investigating this potential mechanism.
Purpose of the Study:
- To investigate the role of glucocorticoid receptors (GR) in mediating enzalutamide resistance in prostate cancer.
- To evaluate the effect of GR modulation on enzalutamide efficacy in preclinical models.
- To explore the correlation between GR expression and clinical response to enzalutamide.
Main Methods:
- In vitro studies using prostate cancer cell lines.
- In vivo xenograft animal models.
- Analysis of GR expression in patient-derived prostate cancer specimens.
Main Results:
- Glucocorticoid receptor (GR) is upregulated in prostate cancer cell lines under specific conditions.
- Dexamethasone (a GR agonist) reversed enzalutamide-induced growth inhibition in preclinical models.
- GR agonists induced androgen receptor target genes, including prostate-specific antigen.
- A correlation was observed between GR expression in patient samples and clinical response to enzalutamide.
Conclusions:
- Preclinical data suggest a potential role for glucocorticoid receptors (GR) in mediating enzalutamide resistance in prostate cancer.
- These findings warrant further investigation into the clinical relevance of GR in castration-resistant prostate cancer (CRPC) treatment.
- Current clinical evidence directly linking GR to CRPC progression or drug resistance remains limited.
