Related Experiment Video
Updated: Sep 22, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment
Zejie Mei1, Tao Yang2, Ying Liu2
1State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Abstract:
Novel strategies for prostate cancer therapy are required to overcome resistance to abiraterone and enzalutamide. Here, we show that increasing 3βHSD1 after abiraterone and enzalutamide treatment is essential for drug resistance, and biochanin A (BCA), as an inhibitor of 3βHSD1, overcomes drug resistance. 3βHSD1 activity increases in cell lines, biopsy samples, and patients after long-term treatment with enzalutamide or abiraterone. Enhanced steroidogenesis, mediated by 3βHSD1, is sufficient to impair enzalutamide function. In patients, accelerated abiraterone metabolism results in a decline of plasma abiraterone as disease progresses. BCA inhibits 3βHSD1 and suppresses prostate cancer development alone or together with abiraterone and enzalutamide. Daidzein, a BCA analog of dietary origin, is associated with higher plasma abiraterone concentrations and prevented prostate-specific antigen (PSA) increases in abiraterone-resistant patients. Overall, our results show that 3βHSD1 is a promising target to overcome drug resistance, and BCA suppresses disease progression as a 3βHSD1 inhibitor even after abiraterone and enzalutamide resistance.
Insights
Increasing 3βHSD1 enzyme activity drives resistance to prostate cancer drugs abiraterone and enzalutamide. Biochanin A (BCA), a 3βHSD1 inhibitor, effectively overcomes this resistance, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Prostate cancer therapy often involves abiraterone and enzalutamide.
- Resistance to these treatments is a significant clinical challenge.
- Novel therapeutic strategies are crucial to overcome treatment resistance.
Purpose of the Study:
- To investigate the role of 3βHSD1 in abiraterone and enzalutamide resistance.
- To evaluate biochanin A (BCA) as a potential therapeutic agent against drug-resistant prostate cancer.
- To explore dietary compounds as adjuncts in prostate cancer treatment.
Main Methods:
- Assessed 3βHSD1 activity in prostate cancer cell lines, patient biopsies, and patient samples after treatment.
- Investigated the effect of BCA on 3βHSD1 activity and prostate cancer progression in vitro and in vivo.
- Analyzed plasma concentrations of abiraterone in patients treated with daidzein, a BCA analog.
Main Results:
- 3βHSD1 activity significantly increases following abiraterone and enzalutamide treatment, contributing to drug resistance.
- Enhanced steroidogenesis mediated by 3βHSD1 impairs enzalutamide efficacy.
- BCA inhibits 3βHSD1, suppressing prostate cancer growth alone or in combination with standard therapies.
- Accelerated abiraterone metabolism was observed in resistant patients.
- Daidzein intake correlated with higher abiraterone levels and prevented PSA increase in resistant patients.
Conclusions:
- 3βHSD1 is a key mediator of resistance to abiraterone and enzalutamide in prostate cancer.
- BCA is a promising 3βHSD1 inhibitor for overcoming acquired resistance and suppressing disease progression.
- Dietary compounds like daidzein may enhance the efficacy of existing therapies.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:30Urinary Tract Calculi III: Medical Management