Relugolix
Brand Name: Orgovyx
Relugolix is used to treat adult patients with advanced prostate cancer.1
How Does Relugolix Work?
Testosterone is a hormone that promotes the development and maintenance of male sexual organs, including the prostate.2 Testosterone is also implicated in a variety of prostate-associated diseases. One such disease is prostate cancer, which commonly depends on testosterone for its survival and growth.3,4
In our body, testosterone production is mediated by the hypothalamic–pituitary–gonadal (HPG) axis. This stepwise process begins with neurons in the hypothalamus of the brain, which release a hormone called GnRH. GnRH is transported to the pituitary gland where cells have GnRH receptors on their surface. When GnRH binds to GnRH receptors, these cells release a set of hormones called FSH and LH. FSH and LH is then transported to the gonad, in this case the testes, and stimulates the production of testosterone.5
Because the HPG axis is the major source of testosterone in the body, blocking this axis can significantly reduce the testosterone available to prostate cancer cells.6 Relugolix is a drug that binds to GnRH receptors in the pituitary gland, but unlike GnRH, relugolix inhibits this receptor.7 As a result, the cells of the pituitary gland do not release FSH and LH, and testosterone production in the gonad is halted.
Ultimately, the depletion of testosterone halts the growth of testosterone-dependent prostate cancer cells and results in their death.8
References
1. ORGOVYX. U.S. Food and Drug Administration (2020).
2. Mooradian, A. D., Morley, J. E. & Korenman, S. G. Biological Actions of Androgens. Endocrine Reviews 8(1), 1-28 (1987).
3. Huggins, C. & Hodges, C. V. Studies on Prostatic Cancer. I. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate. Cancer Research 1(4), 293-297 (1941).
4. Dehm, S. M. & Tindall, D. J. Androgen Receptor Structural and Functional Elements: Role and Regulation in Prostate Cancer. Molecular Endocrinology 21(12), 2855-2863 (2007).
5. Jin, J. & Yang, W. Molecular regulation of hypothalamus-pituitary-gonads axis in males. Gene 551(1), 15-25 (2014).
6. Waxman, J. H. et al. Treatment with gonadotrophin releasing hormone analogue in advanced prostatic cancer. British Medical Journal (Clinical research ed.) 286, 1309-1312 (1983).
7. Nakata, D. et al. Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: Studies in human GnRH receptor knock-in mice. European Journal of Pharmacology 723, 167-174 (2014).
8. Akakura, K. et al. Effects of intermittent androgen suppression on androgen-dependent tumors. Apoptosis and serum prostate-specific antigen. Cancer 71(9), 2782-2790 (1993).
