CYP17A1 inhibitors

CYP17A1 inhibitors are a class of drugs that target the cytochrome P450 17A1 (CYP17A1) enzyme, a critical enzyme in the production of steroids, including androgens and estrogens. These inhibitors are primarily used in the treatment of prostate cancer, as well as in certain cases of breast cancer and Cushing's syndrome. By inhibiting the CYP17A1 enzyme, these drugs reduce the production of androgens, which can fuel the growth of prostate cancer cells.

Mechanism of Action

CYP17A1 inhibitors work by binding to the CYP17A1 enzyme, which is involved in two key steps of steroidogenesis: 17α-hydroxylase and 17,20-lyase activities. These activities are crucial for the production of glucocorticoids, mineralocorticoids, androgens, and estrogens. By inhibiting this enzyme, CYP17A1 inhibitors reduce the synthesis of androgens such as testosterone and dihydrotestosterone (DHT), which are known to promote the growth of prostate cancer cells.

Clinical Uses

The primary use of CYP17A1 inhibitors is in the treatment of prostate cancer. These drugs are particularly useful in cases where the cancer has become resistant to traditional androgen deprivation therapy (ADT). They are also being investigated for their potential use in treating breast cancer that is sensitive to hormones, as well as in managing the symptoms of Cushing's syndrome by reducing cortisol levels.

Examples of CYP17A1 Inhibitors

• Abiraterone acetate – One of the most widely used CYP17A1 inhibitors, often used in combination with a corticosteroid to manage metastatic, castration-resistant prostate cancer.
• Ketoconazole – An antifungal medication that also has properties of CYP17A1 inhibition, used off-label for prostate cancer treatment, especially before more specific inhibitors were available.

Side Effects

The inhibition of CYP17A1 can lead to a decrease in the production of not only androgens but also other steroids, including glucocorticoids and mineralocorticoids. This can result in side effects such as:

• Hypertension
• Hypokalemia
• Fluid retention
• Adrenal insufficiency
• Liver toxicity

Patients on CYP17A1 inhibitors often require monitoring and may need supplemental corticosteroids to mitigate some of these side effects.

Future Directions

Research is ongoing to develop new CYP17A1 inhibitors with greater specificity and fewer side effects. Additionally, studies are exploring the combination of these inhibitors with other therapies, such as chemotherapy and radiation, to enhance treatment efficacy in prostate and breast cancer.

See Also

• Steroidogenesis
• Prostate cancer
• Breast cancer
• Cushing's syndrome
• Androgen deprivation therapy