Abiraterone acetate is an orally administered potent inhibitor of cytochrome P450 17α-hydroxylase/C17,20-lyase (CYP17), which is essential for the synthesis of testosterone from cholesterol
. It is used in the treatment of metastatic castration-resistant prostate cancer (mCRPC)
Mechanism of action
- CYP17 inhibition: Abiraterone inhibits CYP17, a critical enzyme in androgen biosynthesis, thereby reducing testosterone levels
- Androgen receptor antagonism: Besides CYP17 inhibition, abiraterone acts as an antagonist to the androgen receptor, potentially contributing to its antitumor effects
- 3β-hydroxysteroid dehydrogenase inhibition: Abiraterone also inhibits 3β-hydroxysteroid dehydrogenase, which may contribute to its antitumor effects
Clinical use
- Metastatic castration-resistant prostate cancer: Abiraterone is used in the treatment of mCRPC, both in patients who have received prior chemotherapy and those who are chemotherapy-naive
- Combination therapy: It is often used in combination with prednisone and can be combined with other agents such as enzalutamide or olaparib, depending on the patient's specific genetic mutations and treatment history
Efficacy
- Overall survival: Abiraterone has been shown to improve overall survival in patients with mCRPC
- Progression-free survival: It has also been associated with improved radiographic progression-free survival
Adverse effects
- Mineralocorticoid excess: The inhibition of the 17α-hydroxylase activity of CYP17 can lead to secondary mineralocorticoid excess
- Cardiac disorders: Abiraterone is associated with an increased incidence of cardiac disorders
In conclusion, abiraterone is an inhibitor of CYP17 used in the treatment of mCRPC, with demonstrated efficacy in improving overall and progression-free survival. However, its use is associated with certain adverse effects, including mineralocorticoid excess and cardiac disorders