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Updated: Aug 30, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
[From the gene to the clinic: prostate cancer death can now be an exception?]
Fernand Labrie1, Leonello Cusan, José Luis Gomez
1Centre de recherche en endocrinologie moléculaire et oncologique, Centre de recherche du CHUL, Centre Hospitalier de l'Université Laval et Université Laval, Sainte-Foy, Québec, G1V 4G2 Canada. fernand.labrie@crchul.ulaval.ca
Abstract:
The most significant discovery of the second half of the XXth century in the field of prostate cancer therapy is probably the observation that the human prostate, as well as many other peripheral human tissues, synthesize locally an important amount of androgens from the inactive steroid precursors dehydroepiandrosterone (DHEA) and its sulfate DHEA-S. In parallel with these observations, two important discoveries also made by our group are applied in the clinic worldwide, namely the use of LHRH (luteininizing hormone-releasing hormone) agonists to completely block testicular androgens, while, simultaneously, the androgens made locally in the prostate from DHEA are blocked in their access to the androgen receptor by a pure antiandrogen of the class of flutamide. This treatment, called combined androgen blockade, has been the first treatment demonstrated to prolong life in prostate cancer. While the first studies were performed in patients with advanced and metastatic disease, our recent data indicate a remarkable level of efficacy of the same treatment applied to localized prostate cancer, namely a 90% possibility of cure. However, in order to be able to treat localized prostate cancer, early diagnosis must be achieved. In the first large-scale randomized study of prostate cancer screening, we have demonstrated that 99% of prostate cancers can be diagnosed at the localized or potentially curable stage, using simple annual measurement of PSA (prostatic specific antigen). Today's data show that with the simple application of the available diagnostic and therapeutic tools, death from prostate cancer should be an exception.
Insights
Early prostate cancer detection using PSA screening and combined androgen blockade therapy significantly improves survival. This approach offers a 90% cure rate for localized disease, making prostate cancer death preventable.
Area of Science:
- Endocrinology and Oncology
- Prostate Cancer Therapeutics
Context:
- Discovery of local androgen synthesis in the prostate from dehydroepiandrosterone (DHEA) and DHEA-S.
- Development of Luteinizing Hormone-Releasing Hormone (LHRH) agonists to suppress testicular androgens.
- Identification of flutamide as a pure antiandrogen blocking prostate androgen receptors.
Purpose:
- To introduce combined androgen blockade (CAB) therapy for prostate cancer.
- To evaluate the efficacy of CAB in advanced, metastatic, and localized prostate cancer.
- To assess the impact of prostate-specific antigen (PSA) screening on early diagnosis.
Summary:
- Combined androgen blockade (CAB), utilizing LHRH agonists and flutamide, effectively treats prostate cancer by blocking both testicular and locally synthesized androgens.
- CAB has demonstrated life-prolonging benefits in advanced prostate cancer and shows a 90% cure rate for localized disease.
- Annual prostate-specific antigen (PSA) screening enables diagnosis of 99% of prostate cancers at a localized, curable stage.
Impact:
- Combined androgen blockade is the first treatment proven to prolong survival in prostate cancer patients.
- Early diagnosis through PSA screening allows for curative treatment of nearly all prostate cancers.
- The combination of effective screening and therapy can make death from prostate cancer an exceptional outcome.
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