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Updated: Apr 29, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Progress in the treatment of advanced prostate cancer
Cora N Sternberg1, Daniel P Petrylak1, Ravi A Madan1
1From the San Camillo Forlanini Hospital, Rome, Italy; Yale University Cancer Center, New Haven, CT; Center for Cancer Research, National Cancer Institute, Bethesda, MD; The Royal Marsden Hospital, London, United Kingdom.
Abstract:
The androgen receptor (AR) is the most significant target for patients with metastatic castration-resistant prostate cancer (mCRPC). There is now irrefutable evidence that the AR axis is functional in most patients throughout the history of prostate cancer, is crucial from diagnosis to death, even in patients who have received hormonal manipulation, and represents a relevant therapeutic target in all phases of the disease. The potential mechanisms of tumor escape after castration are multifold, with each mechanism today representing a therapeutic opportunity. Phase III trials have been able to demonstrate improved overall survival (OS), improved quality of life, decreased skeletal-related events, and other important clinical benefits in young and elderly patients. After the initial positive results with docetaxel chemotherapy in improving OS, further research has resulted in five new treatments in the past few years. Immunotherapy with sipuleucel-T, cabazitaxel chemotherapy, the androgen biosynthesis inhibitor abiraterone acetate, the antiandrogen enzalutamide, and the radioisotope radium-223 have all been shown to improve OS in large-scale, well-conducted clinical trials. Proper understanding of mechanisms of resistance and of cross-resistance among these agents, sequencing, and combinations is now a priority.
Insights
The androgen receptor (AR) pathway remains critical in metastatic castration-resistant prostate cancer (mCRPC). New treatments targeting AR and resistance mechanisms offer improved survival and quality of life for patients.
Area of Science:
- Oncology
- Urology
- Medical Research
Background:
- The androgen receptor (AR) axis is a critical target in metastatic castration-resistant prostate cancer (mCRPC).
- AR signaling remains active throughout the disease course, even after hormonal manipulation.
- Understanding tumor escape mechanisms is key to developing new therapeutic strategies.
Purpose of the Study:
- To review the significance of the AR axis as a therapeutic target in mCRPC.
- To discuss the evolution of treatment strategies and emerging therapies.
- To highlight the importance of understanding resistance mechanisms for optimizing treatment sequencing and combinations.
Main Methods:
- Review of Phase III clinical trial data.
- Analysis of established and novel therapeutic agents for mCRPC.
- Discussion of the role of the androgen receptor pathway in prostate cancer progression.
Main Results:
- Multiple new treatments, including chemotherapy, immunotherapy, androgen biosynthesis inhibitors, antiandrogens, and radioisotopes, have demonstrated improved overall survival (OS).
- These agents offer clinical benefits such as improved quality of life and reduced skeletal-related events.
- The AR axis is a validated therapeutic target across all stages of prostate cancer.
Conclusions:
- The androgen receptor pathway is a central target in mCRPC, with significant clinical benefits demonstrated by various therapeutic modalities.
- Understanding resistance and cross-resistance mechanisms is crucial for effective treatment sequencing and combination strategies.
- Ongoing research into AR-targeted therapies and resistance mechanisms continues to improve outcomes for mCRPC patients.
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