Prostate cancer (PCa) is a prevalent and life-threatening disease among men, ranking as the second most common cancer and the fifth leading cause of cancer-related death. in fact, androgen deprivation therapy (ADT) is a main approach for patients with advanced disease. For metastatic PCa, ADT with a gonadotropin-releasing hormone (GnRH) antagonist/agonist, followed by treatment with docetaxel plus prednisolone, and continued ADT after disease progression has become the standard treatment.

GnRH, also known as luteinizing hormone-releasing hormone (LHRH), plays a crucial role in controlling the hypothalamic-pituitary-axis in mammals. It binds to the GnRH receptor (GnRHR) and stimulates the release of luteinizing hormone (LH), which triggers testosterone synthesis in the Leydig cells of the testes. In PCa treatment, the goal is to suppress the release of LH and testosterone, as they fuel the growth of cancer cells.

Long-acting GnRH agonists inhibit the release of LH and testosterone. Unlike GnRH agonists, GnRH antagonists bind competitively to GnRHR in the pituitary gland. Then it rapidly blocks LH production, thereby suppressing testosterone to castration levels. Abarelix is the first GnRH antagonist approved by the FDA.

Abarelix is a potent GnRH antagonist, used for prostate cancer research.

Firstly, Abarelix (R3827; PPI 149) can produce rapid and sustained decreases in testosterone to castrate levels without the need for co-administration of an antiandrogen. And it has a very low complication rate in the short term.

Secondly, Abarelix (30 and 300 µg/mL) causes significantly increased histamine release. Thirdly, Abarelix demonstrates to promptly and substantially reduce follicle-stimulating hormone levels to lower than LHRH agonist. Meanwhile, Abarelix does not cause a surge in serum testosterone. The high level of serum testosterone can precipitate a flare phenomenon or worsening of disease, particularly dangerous for patients with metastatic, symptomatic disease.

References:

[1] He Y, et al. Signal Transduct Target Ther. 2022 Jun 24;7(1):198.

[2] Kirby RS, et al. BJU Int. 2009 Dec;104(11):1580-4.

[3] Debruyne F, et al. Future Oncol. 2006 Dec;2(6):677-96.