Description:
Background
Androgen receptor activity, mediated by androgens like dihydrotestosterone (DHT), is a key driver of prostate cancer (PCa). Although hormonal therapy remains the cornerstone of PCatreatment, patient responses are highly variable, and it remains difficult to reliably predict who will benefit. Developing predictive biomarkers and accessible diagnostic assays is therefore critical for optimizing hormonal therapy and improving patient outcomes.
Innovation
USC researchers have identified germline SRD5A variants that predict response to hormonal therapy in patients with metastatic castration-sensitive PCa. SRD5A genes encode for the steroid 5α-reductase isoenzymes, which catalyze the production of the potent androgen, DHT. Genotyping analysis was performed on 41 variants in the SRD5A1, SRD5A2, and SRD5A3genes. In a multi-center cohort of 364 patients undergoing hormonal therapy, those with an SRD5A variant had shorter progression free survival, shorter overall survival, and were less likely to achieve a complete PSA response. These findings highlight SRD5A variants as key predictors of hormonal therapy response and support their potential application in guiding treatment decisions for metastatic PCa.
Advantages
- Enables earlier identification of patients who may not respond to hormonal therapy alone
- Germline variants can be assayed using readily available sample types and standard genotyping platforms
Stage of Development
- Initial analysis done in 364 patient metastatic PCa cohort
- Biomarker validation planed in additional patient cohorts
- Validation of PCR-based assay is underway