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Updated: Mar 6, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Targeting androgen receptor versus targeting androgens to suppress castration resistant prostate cancer
Changcheng Guo1, Shuyuan Yeh2, Yuanjie Niu3
1Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
Abstract:
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941. Multiple strategies related to surgical/chemical castration with combinations of various anti-androgens, including Cyproterone Acetate, Flutamide, Nilutamide, Bicalutamide (Casodex) and Enzalutamide, as well as some androgen synthesis blockers, including Abiraterone, have been used to control PCa progression. However, patients on ADT with anti-androgen treatment eventually develop resistance, which might be accompanied with the unwanted side effects of enhanced metastasis. New therapeutic approaches via directly targeting the AR with ASC-J9®, Cisplatin, EPI-001, Niclosamide, and VPC compounds as well as silencing AR with siRNAs or non-coding RNAs have been developed to further suppress PCa at the castration resistant stages.
Insights
Prostate cancer progression is linked to androgen signaling. While androgen deprivation therapy (ADT) is standard, resistance develops. New therapies target the androgen receptor (AR) to overcome resistance and reduce metastasis.
Area of Science:
- Oncology
- Endocrinology
Background:
- Prostate cancer (PCa) is a leading cause of cancer death in men, driven by androgen/androgen receptor (AR) signaling.
- Hormonal factors like castration and 5α-reductase deficiency prevent PCa, highlighting the role of androgens.
- Androgen deprivation therapy (ADT) has been the primary treatment for advanced PCa since 1941.
Purpose of the Study:
- To review current therapeutic strategies for advanced prostate cancer.
- To discuss the development of resistance to androgen deprivation therapy (ADT).
- To explore novel therapeutic approaches targeting the androgen receptor (AR) for castration-resistant prostate cancer.
Main Methods:
- Review of established and emerging treatments for prostate cancer.
- Analysis of therapeutic resistance mechanisms in advanced PCa.
- Identification of novel compounds and RNA-based strategies targeting the AR pathway.
Main Results:
- ADT, including castration and anti-androgens (e.g., Bicalutamide, Enzalutamide), controls PCa but often leads to resistance.
- Resistance to ADT can be associated with increased metastasis.
- Emerging therapies include direct AR inhibitors (e.g., ASC-J9®, EPI-001) and AR silencing techniques (siRNAs, non-coding RNAs).
Conclusions:
- Androgen receptor (AR) signaling is crucial in prostate cancer (PCa) progression and treatment resistance.
- Novel therapeutic strategies are essential to overcome resistance to current androgen deprivation therapy (ADT).
- Targeting the AR directly or silencing it offers promising avenues for treating castration-resistant prostate cancer (CRPC).
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