Fernand Labrie was the first to isolate a mammalian messenger RNA, namely rabbit hemoglobin messenger RNA in 1968-1969. He then performed its partial nucleotide sequencing during his postdoctoral training in the laboratory of Professor Frederick Sanger, twice a Nobel laureate, at the Laboratory of Molecular Biology in Cambridge, United Kingdom. Following his return to Laval University in Quebec City, Canada in 1969, a major discovery was made by Doctor Labrie with immediate application to the treatment of prostate cancer – namely medical castration with GnRH (Gonadotropin-Releasing Hormone) agonists which achieve a complete and reversible chemical castration in men. The exceptional efficacy and tolerance of medical castration achieved with GnRH agonists rapidly led to the worldwide replacement of orchiectomy and high doses of estrogens for the treatment of prostate cancer.
This highly successful transfer of a fundamental research observation to the establishment of medical castration in prostate cancer was rapidly followed by the discovery that adding an antiandrogen to castration permits blockade of the action of the androgens made locally in the prostate from the inactive precursor of sex steroids, namely dehydroepiandrosterone (DHEA) of adrenal origin. Such a strategy simultaneously blocks both sources of androgens of approximately equal importance which stimulate prostatic tumor growth, namely the testosterone secreted by the testicles and the androgens made locally in the prostate from DHEA. This approach called combined androgen blockade (CAB) was the first treatment shown to prolong life in prostate cancer and has become the standard hormonal therapy for prostate cancer worldwide. This discovery has permitted the successful commercialization of the antiandrogens flutamide, bicalutamide and nilutamide and is at the basis of the successful development of enzalutamide and abiraterone acetate as inhibitors of the action and formation, respectively, of androgens in prostate cancer.
Fernand Labrie and his group also performed the first prospective, randomized clinical trial of prostate cancer screening. This study hastened the development of a strategy to detect prostate cancer at an early and potentially curable stage in more than 95% of cases, thus practically eliminating the diagnosis of advanced prostate cancer at the metastatic and non-curable stage.
While up to 50% of androgens in men are made in peripheral tissues from the precursor DHEA, DHEA is even more important in women since all estrogens and all androgens after menopause are made in peripheral tissues from DHEA by the mechanisms of intracrinology. Accordingly, before the work of Professor Labrie on intracrinology, the lack of estrogens starting at menopause was believed to be the cause of all the problems related to hormone deficiency after menopause. Accordingly, estrogens were exclusively used as replacement therapy for the symptoms of menopause with their potential side effects illustrated in the Women’s Health Initiative (WHI) study. Working with the knowledge obtained from intracrinology, Professor Labrie discovered that the relative lack of DHEA and not the lack of estrogens is responsible for the menopausal symptoms secondary to hormone deficiency after menopause. Accordingly, under his leadership, Endoceutics™ has completed the clinical development of Intrarosa™ which has been approved for commercialization in November 2016 by the US FDA for the treatment of dyspareunia or pain at sexual activity, a symptom of vulvovaginal atrophy due to menopause. This novel treatment has been approved without a black box warning or without safety concerns.