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Updated: Mar 29, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Androgen-glucocorticoid interactions in the era of novel prostate cancer therapy
Sujata Narayanan1, Sandy Srinivas1, David Feldman2
1Stanford Cancer Centre, 875 Blake Wilbur Drive, Stanford, California 94305, USA.
Abstract:
Great strides have been made in the treatment of castration-resistant prostate cancer (CRPC) with the development of new antiandrogens (enzalutamide) and more potent androgen synthesis inhibitors (abiraterone) that have both improved patient outcomes. These new drugs have also helped unravel the complex biology of androgen-androgen receptor driven prostate cancer and brought into prominence various mechanisms triggering the development of drug resistance and tumour cell survival despite use of androgen deprivation therapy (ADT). The complex role of glucocorticoids in the treatment, management and progression of patients with CRPC is integral to these advances. Historically, glucocorticoid treatment has resulted in both subjective and objective responses in patients with advanced-stage prostate cancer. With the use of these new therapeutic agents, however, unexpected glucocorticoid-related mechanisms that can cause iatrogenic stimulation of prostate cancer growth have emerged, which might contribute to drug resistance and disease progression despite optimal ADT. For example, the upregulation of glucocorticoid receptors (GRs) during enzalutamide therapy results in glucocorticoid-GR-mediated regulation of androgen target genes, leading to escape from enzalutamide blockade. Thus, understanding the biological role of glucocorticoids in patients with prostate cancer is of major importance in the era of new and evolving antiandrogen therapies.
Insights
New antiandrogen therapies for castration-resistant prostate cancer (CRPC) reveal glucocorticoids can paradoxically fuel tumor growth. Understanding this glucocorticoid-CRPC interaction is crucial for effective treatment strategies.
Area of Science:
- Oncology
- Endocrinology
- Cancer Biology
Background:
- Advanced castration-resistant prostate cancer (CRPC) treatments, including enzalutamide and abiraterone, have improved outcomes.
- These therapies illuminate the androgen-androgen receptor pathway and resistance mechanisms in prostate cancer.
- Glucocorticoids have historically shown therapeutic benefits in advanced prostate cancer.
Purpose of the Study:
- To investigate the complex role of glucocorticoids in CRPC progression.
- To understand how glucocorticoids may contribute to drug resistance and tumor survival despite androgen deprivation therapy (ADT).
- To explore glucocorticoid-receptor mediated mechanisms that promote cancer growth during novel antiandrogen therapies.
Main Methods:
- Review of current literature on CRPC treatment and glucocorticoid interactions.
- Analysis of emerging mechanisms of drug resistance related to glucocorticoid signaling.
- Examination of glucocorticoid receptor (GR) upregulation and its effect on androgen target genes.
Main Results:
- Novel antiandrogen therapies have uncovered unexpected glucocorticoid-driven prostate cancer stimulation.
- Upregulation of glucocorticoid receptors (GRs) can mediate androgen target gene expression, leading to resistance to therapies like enzalutamide.
- Glucocorticoid-related mechanisms may drive disease progression even with optimal ADT.
Conclusions:
- Understanding the biological role of glucocorticoids is critical in the context of evolving antiandrogen therapies for CRPC.
- Glucocorticoid-mediated pathways represent a significant factor in treatment resistance and disease progression.
- Further research into glucocorticoid-prostate cancer interactions is essential for optimizing therapeutic strategies.
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