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Science behind total androgen blockade: from gene to combination therapy
F Labrie1, A Bélanger, A Dupont
1Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Québec City, Québec.
Summary
Adrenal glands and testicles produce equal amounts of dihydrotestosterone (DHT), crucial for prostate cancer growth. Blocking DHT from both sources with combination therapy prolongs life in advanced prostate cancer.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Dihydrotestosterone (DHT) is the active androgen stimulating prostate cell growth.
- Both testicles and adrenal glands contribute significantly to DHT production.
Purpose of the Study:
- To investigate the role of adrenal precursors in prostate cancer.
- To evaluate combination therapy for advanced prostate cancer.
Main Methods:
- Elucidation of enzyme structures involved in DHT synthesis from dehydroepiandrosterone (DHEA).
- Combination therapy involving orchiectomy/LHRH agonist and pure antiandrogen.
Main Results:
- DHT is formed locally in the prostate from circulating adrenal DHEA.
- Combination therapy prolongs survival in advanced prostate cancer.
- Combination therapy may improve curative treatment efficacy for early-stage disease.
Conclusions:
- Adrenal glands play a critical role in prostate cancer endocrine therapy.
- Combination therapy targeting both testicular and adrenal androgens is essential.
- This approach offers improved outcomes for advanced and potentially early-stage prostate cancer.