# Racial Disparity in the Expression of Androgen Receptor Splice Variants (AR-SVs) in Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $228,000

## Abstract

Approximately 174,000 men in the United States were diagnosed with prostate cancer (PCa) and approximately
31,000 died of PCa in 2019. The number of PCa survivors is expected to increase from 3.3 million men currently
to 4.5 million by 2026. One of the primary reasons for treatment failure and castration-resistant prostate cancer
(CRPC) relapse is expression of constitutively-active AR splice variants (AR-SVs) that lack the ligand binding
domain (LBD) and thus remain constitutively active. AR-SVs contribute to an aggressive phenotype of CRPC,
shorter progression-free survival (PFS), and failure to respond to enzalutamide or abiraterone. Compared to
Caucasian men, African American men have a 63% higher overall PCa incidence (228.8 vs 140.3 per 100,000,
age adjusted to 2000 US population). These patients are more likely to be diagnosed with aggressive/potentially
lethal PCa, are 2.44-fold more likely to die from PCa and have shorter disease-free survival. Our central
hypothesis is that the higher incidence of aggressive CRPC in African American men is due to the higher
expression and function of AR-SVs compared to their Caucasian counterparts. As our SARDs are the only
set of molecules having the properties to degrade the AR-SVs, proving this hypothesis will help us to tailor our
drug development protocols towards the African American men who might have higher expression of AR-SVs.
To address the hypothesis that the African American men express AR-SVs at a higher level than Caucasian
men, we will determine the expression of AR-V7 in PCa and CRPC specimens from African American and
Caucasian men (specific aim-1), determine race differences in AR-V7 function by quantifying AR-V7-target gene
signature expression in PCa tissue from African American and Caucasian PCa patients (specific aim-2), and test
the efficacy of SARDs in CRPC patient-derived xenograft UT-1335 that was obtained from an African American
man (specific aim-3). The data will be a harbinger for future drug development tailored towards African American
men with PCa.

## Key facts

- **NIH application ID:** 10099535
- **Project number:** 3R01CA229164-02S2
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Ramesh Narayanan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,000
- **Award type:** 3
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10099535

## Citation

> US National Institutes of Health, RePORTER application 10099535, Racial Disparity in the Expression of Androgen Receptor Splice Variants (AR-SVs) in Prostate Cancer (3R01CA229164-02S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10099535. Licensed CC0.

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