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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
The development of abiraterone acetate for castration-resistant prostate cancer
Emily Grist1, Gerhardt Attard1
1The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK.
Abstract:
Abiraterone acetate is a novel CYP17A1 inhibitor demonstrated to prolong survival in castration-resistant prostate cancer (CRPC). This review explores key stages in the almost 20-year history of abiraterone acetate׳s development, starting with a program aiming to develop inhibitors of androgen synthesis at the Institute of Cancer Research, London. Clinical development was initially slow owing to insufficient data supporting targeting of androgen synthesis as a therapeutic approach in CRPC and safety concerns of adrenocortical insufficiency from suppression of cortisol. Regulatory authorities approved abiraterone acetate in 2011 after a survival benefit was demonstrated when given in combination with prednisone as compared with prednisone alone in docetaxel-treated men. Licensing approval extended to include chemotherapy-naive patients with CRPC in 2012 following a significant increase in radiographic progression-free survival. Ongoing research focuses on identifying predictive biomarkers and understanding mechanisms of resistance to improve its administration.
Insights
Abiraterone acetate, a CYP17A1 inhibitor, has significantly improved survival for castration-resistant prostate cancer (CRPC). Its development journey highlights overcoming early challenges to become a vital treatment option.
Area of Science:
- Oncology
- Pharmacology
Background:
- Castration-resistant prostate cancer (CRPC) presents a significant therapeutic challenge.
- Abiraterone acetate targets CYP17A1, inhibiting androgen synthesis, a key driver in prostate cancer progression.
Purpose of the Study:
- To review the historical development of abiraterone acetate for CRPC.
- To outline the key milestones, challenges, and regulatory approvals of abiraterone acetate.
Main Methods:
- Historical review of abiraterone acetate's development.
- Analysis of clinical trial data demonstrating survival benefits.
- Examination of regulatory approval processes.
Main Results:
- Abiraterone acetate demonstrated a survival benefit in docetaxel-treated CRPC patients when combined with prednisone.
- Further approval was granted for chemotherapy-naive CRPC patients based on improved radiographic progression-free survival.
Conclusions:
- Abiraterone acetate is an established therapy for CRPC, prolonging survival.
- Current research focuses on biomarkers and resistance mechanisms to optimize treatment strategies.
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