Beyond castration and chemotherapy: novel approaches to targeting androgen-driven pathways
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Updated: Jun 20, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Sumanta Kumar Pal1, Przemyslaw Twardowski, David Y Josephson
1Division of Genitourinary Malignancies, Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, United States. spal@coh.org
Abstract:
In castrate-resistant prostate cancer, beyond chemotherapy, existing guidelines suggest only supportive care. However, recent evidence suggests that continued targeting of androgen-dependent pathways may be an efficacious approach. Clinical data is now available for two mechanistically distinct agents (abiraterone and MDV3100) that both ultimately target these pathways. Abiraterone is a potent and irreversible inhibitor of CYP17, a critical enzyme in androgen biosynthesis. Phase II studies indicate substantial declines in PSA amongst castrate-resistant patients treated with abiraterone, both prior to and following cytotoxic chemotherapy. In contrast to abiraterone, MDV3100 is a direct inhibitor of the androgen receptor, binding the receptor irreversibly with substantially higher affinity as compared to bicalutamide. A recent phase I/II trial of MDV3100 in castrate-resistant prostate cancer demonstrated tolerability of the agent with activity at the lowest dose level. On the basis of these compelling data, both abiraterone and MDV3100 will be examined in the phase III setting.
Insights
New agents targeting androgen pathways show promise for castrate-resistant prostate cancer (CRPC). Abiraterone and MDV3100 demonstrate efficacy, offering new therapeutic options beyond supportive care for advanced prostate cancer.
Area of Science:
- Oncology
- Urology
- Pharmacology
Background:
- Current guidelines for castrate-resistant prostate cancer (CRPC) recommend supportive care post-chemotherapy.
- Emerging evidence supports targeting androgen-dependent pathways in advanced prostate cancer.
- Abiraterone and MDV3100 are novel agents targeting these pathways.
Purpose of the Study:
- To review clinical data for abiraterone and MDV3100 in CRPC.
- To evaluate the efficacy and tolerability of these novel agents.
- To establish the rationale for further phase III investigation.
Main Methods:
- Review of Phase II studies for abiraterone (CYP17 inhibitor).
- Review of Phase I/II trial for MDV3100 (androgen receptor inhibitor).
- Analysis of prostate-specific antigen (PSA) declines and tolerability data.
Main Results:
- Abiraterone demonstrated significant PSA declines in CRPC patients.
- MDV3100 showed tolerability and activity in early-phase trials.
- Both agents target androgen-dependent pathways effectively.
Conclusions:
- Abiraterone and MDV3100 represent promising therapeutic strategies for CRPC.
- Continued androgen pathway inhibition is a viable approach in advanced prostate cancer.
- Phase III trials are warranted to further assess these agents.
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