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Updated: Jul 5, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Castration-recurrent prostate cancer is not androgen-independent
1Urologic Oncology, University of North Carolina, Chapel Hill, NC, USA.
Abstract:
An American man is diagnosed with prostate cancer (PC) every 3 min and dies from the disease every 17 min. Although androgen receptor (AR) expression is diminished following androgen deprivation therapy (ADT) that induces clinical remission in most patients, castration-recurrent PC expresses levels of AR protein similar to those found in androgen-stimulated PC and benign prostate. This observation suggests that the AR may be as important for growth regulation in castration-recurrent PC, as it is in androgen-stimulated PC and benign hyperplasia. Neither ligand-independence, point mutations, glutamine and/or glycine repeat expansion nor amplification have explained AR activation in most cases of castration-recurrent PC. Castration-recurrent PC tissue has levels of testosterone (T) similar to androgen-stimulated benign prostate and levels of dihydrotestosterone (DHT), the most active androgen for AR activation that are approximately 10% of androgen-stimulated benign prostate. These levels of tissue androgens appear capable of activating the AR since prostate-specific antigen (PSA), the classic androgen-regulated gene, is expressed at similar tissue levels in castration-recurrent and androgen-stimulated PC. These startling findings suggest a paradigm shift; PC that recurs during ADT is not androgen-independent.
Insights
Prostate cancer (PC) recurring during androgen deprivation therapy (ADT) is not androgen-independent. Castration-recurrent PC maintains androgen receptor (AR) activity, suggesting AR remains crucial for disease progression.
Area of Science:
- Oncology
- Urology
- Molecular Biology
Background:
- Prostate cancer (PC) is a significant health concern, with frequent diagnoses and deaths.
- Androgen deprivation therapy (ADT) initially induces remission but often leads to castration-recurrent PC.
- The androgen receptor (AR) remains active in recurrent PC, despite ADT, suggesting continued reliance on AR signaling.
Purpose of the Study:
- To investigate the mechanism of AR activation in castration-recurrent prostate cancer.
- To determine if AR signaling is truly androgen-independent in recurrent PC.
- To challenge the existing paradigm of castration-recurrent PC.
Main Methods:
- Analysis of AR protein levels in castration-recurrent PC compared to androgen-stimulated PC and benign prostate tissue.
- Measurement of tissue androgen levels (testosterone and dihydrotestosterone) in recurrent PC.
- Assessment of prostate-specific antigen (PSA) expression as a marker of AR activity.
Main Results:
- Castration-recurrent PC exhibits AR protein levels comparable to androgen-stimulated PC.
- Tissue androgen levels in recurrent PC are sufficient to activate the AR.
- Prostate-specific antigen (PSA) expression is similar in recurrent and androgen-stimulated PC, indicating AR activation.
Conclusions:
- Prostate cancer that recurs during ADT is not androgen-independent.
- The AR remains a critical target for therapeutic intervention in castration-recurrent PC.
- These findings necessitate a paradigm shift in understanding and treating recurrent prostate cancer.
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