Biochanin A inhibits the activity of androgen receptor mutants to suppress the development of prostate cancer

Vollständiger Abstract

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Androgens and the androgen receptor ( AR ) play a central role in the development and progression of prostate cancer. While biochanin A (BCA) has been reported to suppress androgen synthesis and overcome resistance to abiraterone and enzalutamide, its direct effects on AR , particularly mutant AR , remain unclear. In this study, we systematically investigated the binding affinity and functional impact of BCA on a panel of clinically relevant AR mutations to identify patient subgroups that may benefit from BCA treatment. Our results demonstrated that BCA exhibits high-binding affinity toward the ART877A and ARW741C mutants. Our findings reveal a previously unrecognized mechanism by which BCA directly targets specific AR mutants, in addition to inhibiting androgen biosynthesis. This study provides mechanistic insights into the mutation-selective activity of BCA and supports its potential clinical application in molecularly stratified prostate cancer.