# Race-related alternative splicing: novel targets in prostate cancer

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $347,517

## Abstract

African American (AA) men exhibit 1.6-fold higher incidence and 2.4-fold higher mortality rates from
prostate cancer (PCa) compared to white men. Although much of this disparity remains after controlling for
factors related to social determinants of health, very few studies have used this population-based difference to
identify molecular mechanisms of tumor aggressiveness. The proposed work addresses the urgent need to
interrogate the molecular mechanisms driving the more aggressive PCa biology in AA men across the PCa
progression continuum and to modulate such mechanisms for therapeutic application.
 Our data from evaluating PCa biopsy tissue from AA and white patients has led to the discovery of
alternative splicing as a novel molecular mechanism underlying more aggressive PCa in AA men. Preliminary
analysis has indicated that several of these race-related alternative splicing events track with increased growth
and more aggressive invasion characteristics of PCa in AA men. Additional preliminary work has demonstrated
our capability to generate the first significant collection of PCa patient-derived explants and the first
establishment of PCa patient-derived explants from AA patients.
 We aim to extend our preliminary findings by 1) determining the pattern and frequency of candidate race-
related splice variants across the PCa progression continuum, from localized PCa of varying degrees of
aggressiveness to metastatic castration-resistant PCa, and defining the relationship between these variants and
PCa cell biology, 2) assessing the effects of expression of particular race-related splice variants on mechanistic
and functional biology in population-specific PCa cell lines and developing tools to pharmacologically modulate
race-related oncogenic splice variants for therapeutic application using AA and white PCa cell lines and AA and
white PCa patient-derived explants generated for this study and 3) defining the biological significance of cis-
acting splicing elements and/or trans-acting splicing factors to driving the alternative splicing events specific to
AA PCa.
 The rationale for and impact of this study are that it will further our understanding of the molecular
mechanisms driving PCa disparities and aid in development of novel precision biomarkers for prostate tumor
aggressiveness and/or therapeutic agents against aggressive PCa. Such precision medicine interventions will
reduce PCa disparities for AAs and will likely have impact on a subset of patients of all races with aggressive
PCa. New AA and white PCa bio-specimens, AA and white PCa patient-derived explants and derivative cell lines
and splicing-related materials and methods and tools resulting from the proposed work will be available to the
nationwide cohort of scientists conducting research on PCa disparities.

## Key facts

- **NIH application ID:** 9925752
- **Project number:** 5R01CA220314-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** STEVEN R PATIERNO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,517
- **Award type:** 5
- **Project period:** 2017-07-05 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925752

## Citation

> US National Institutes of Health, RePORTER application 9925752, Race-related alternative splicing: novel targets in prostate cancer (5R01CA220314-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9925752. Licensed CC0.

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