A multimodal liquid biopsy assay to quantify androgen receptor’s somatic alterations in metastatic castration-resistant prostate cancer.

About This Grant

PROJECT SUMMARY The high mortality rate of metastatic prostate cancer underscores the urgent need for a sensitive detection assay for androgen receptor (AR) alterations, which are primary drivers of resistance to AR-targeted therapies in metastatic castrate-resistant prostate cancer (mCRPC). AR alterations, including amplifications, mutations, and splicing variants, are present in 50-70% of mCRPC patients and are associated with worse outcomes, underscoring the importance of targeting AR alterations to optimize treatment and guide personalized therapy. Despite extensive genomic knowledge with the potential to enhance clinical care and guide future clinical trial design, the discoveries of AR alterations in mCRPC have not been translated into clinical practice due to the lack of assay development and implementation. This project aims to bridge this gap by developing and validating a plasma-based multimodal digital PCR assay for AR alterations as a Laboratory Developed Test. In Aim 1, we will determine and validate the analytical performance of the assay by quantifying AR somatic alterations, ensuring its accuracy and reproducibility. In Aim 2, we will establish the clinical utility of the assay by evaluating its prognostic and predictive capabilities in a cohort of mCRPC patients. This minimally invasive liquid biopsy approach will facilitate the monitoring of clonal evolution and treatment resistance, capture genomic heterogeneity across metastatic sites, and provide a cost-effective, sensitive tool for identifying clinically relevant AR alterations that inform personalized therapy, ultimately refining current and future clinical practice in mCRPC and improving patient outcomes.