# Novel ctDNA biomarker for androgen therapy in metastatic prostate cancer

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $596,475

## Abstract

PROJECT SUMMARY
The deadliest form of advanced-stage prostate cancer is treatment-resistant metastatic castration-
resistant prostate cancer (mCRPC), which occurs in ~35% of patients after exposure to androgen
receptor (AR)-directed therapies such as Abiraterone and Enzalutamide, resulting in a dismal median
survival of only ~5.5 months. Unfortunately, detection of treatment-resistant disease typically occurs
too late, when patients are already progressing on AR-directed drugs, after which they succumb rapidly
to their disease. There is therefore a critical need to detect AR resistance more sensitively and earlier
in the disease course. To address this, our team designed a novel cell-free DNA assay called Enhancer
and Neighboring Loci of Androgen Receptor Sequencing (EnhanceAR-Seq), built upon the Cancer
Personalized Profiling by deep Sequencing (CAPP-Seq) platform, and demonstrated superb sensitivity
for detecting AR gene body and enhancer locus alterations in plasma collected from mCRPC patients.
Notably, we applied our EnhanceAR-Seq technology to mCRPC patient plasma and showed that the
results correlate strongly with clinically verified resistance to AR-directed therapy, and significantly
outperform circulating tumor cell (CTC) AR-V7 detection. Building upon this, the current proposal will
evaluate whether our EnhanceAR-Seq technology can be used to predict both (Aim 1) pre-treatment
and (Aim 2) on-treatment resistance to AR-directed therapy in mCRPC patients. Further, in Aim 3 we
will investigate whether integrating EnhanceAR-Seq with genome-wide methylation sequencing can
granularly refine our ability to predict treatment resistance and monitor both clonal and phenotypic
evolution in mCRPC. We are uniquely positioned to accomplish this through our interdisciplinary team
comprised of cell-free DNA genomicists, bioinformaticians, oncologists, and statisticians. Overall, this
study has significant translational impact by establishing cell-free genomic and epigenomic biomarkers
of tumor evolution and resistance to AR-directed therapy in men with lethal prostate cancer.

## Key facts

- **NIH application ID:** 10780794
- **Project number:** 1R01CA286127-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Aadel Chaudhuri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $596,475
- **Award type:** 1
- **Project period:** 2023-12-06 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10780794

## Citation

> US National Institutes of Health, RePORTER application 10780794, Novel ctDNA biomarker for androgen therapy in metastatic prostate cancer (1R01CA286127-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10780794. Licensed CC0.

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