Prospective role of 3βHSD1 in prostate cancer precision medicine

by Selleckchem | Mar 20 2023

Background: Prostate cancer is addicted to androgens. The steroidogenic enzyme 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) recognizes pregnenolone, dehydroepiandrosterone (DHEA), and steroidal medicine abiraterone as substrates to accelerate disease progression.

Methods: References for this review were identified through searches of PubMed with the search terms "prostate cancer", "HSD3B1", and "3bHSD1" from 1990 until June, 2022.

Results: Genotype of 3βHSD1 has been reported to correlate with tumor aggressiveness of advanced prostate cancer in multiple clinical scenarios. The ethnic differences and limitations of using 3βHSD1 genotype as a prognostic biomarker have been discussed here. The activity of 3βHSD1 increases in patients treated with abiraterone and enzalutamide, giving rise to treatment resistance. Further elucidation of 3βHSD1 regulatory mechanisms will shed light on more approaches for disease intervention. We also review the recent advance on 3βHSD1 inhibitors and targeting 3βHSD1 for prostate cancer management. Novel 3βHSD1 inhibitors will be needed to provide additional options for prostate cancer management.

Conclusion: 3βHSD1 is both a predictive biomarker and a promising therapeutic target for prostate cancer.

Comments：

Prostate cancer is a hormone-dependent cancer that is addicted to androgens for growth and survival. The steroidogenic enzyme 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) plays a critical role in the biosynthesis of androgens by converting pregnenolone and dehydroepiandrosterone (DHEA) to testosterone and dihydrotestosterone (DHT), respectively. 3βHSD1 has been identified as a potential therapeutic target for the treatment of advanced prostate cancer, as well as a biomarker for predicting disease aggressiveness and treatment response.

Studies have shown that the genotype of 3βHSD1 is associated with tumor aggressiveness and clinical outcomes in patients with advanced prostate cancer. However, the use of 3βHSD1 genotype as a prognostic biomarker is limited by ethnic differences and other factors that may affect the accuracy of the test.

The use of steroidal medicines, such as abiraterone and enzalutamide, in the treatment of advanced prostate cancer can increase the activity of 3βHSD1, leading to treatment resistance. Therefore, the development of novel 3βHSD1 inhibitors is crucial for improving the effectiveness of current treatments and providing additional options for prostate cancer management.

Recent advances in the development of 3βHSD1 inhibitors have shown promising results in preclinical studies. Further elucidation of the regulatory mechanisms of 3βHSD1 will provide a better understanding of its role in prostate cancer progression and identify new approaches for disease intervention.

In conclusion, 3βHSD1 is a potential therapeutic target and predictive biomarker for prostate cancer. The development of novel 3βHSD1 inhibitors and the elucidation of its regulatory mechanisms will provide new opportunities for prostate cancer management.