# Parp Function in Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $373,908

## Abstract

ABSTRACT
The androgen receptor (AR) makes profound contributions to the biology of prostate
cancer cells, principally through its function as a ligand-regulated transcription factor. As
such, therapeutic approaches to prostate cancer are typically designed to deplete or
compete with endogenous androgens with the goal of reducing the transcription function
of AR. This proposal addresses a relatively unexplored area of AR action, which is how it
generates and responds to DNA damage. In brief, we have developed a large set of
preliminary data that shows AR is part of an signaling axis that is initiated by androgen,
requires inputs from the DNA damage and repair machinery, and results in assembly of
a DNA repair complex. We found that one of the key enzymes in this pathway is Parp7,
a mono-ADP-ribosytransferase for which little is known. In Aim1 we will determine how
Parp7 is regulated by androgen and DNA damage signaling in prostate cancer cells. In
Aim2 we will determine how Parp7 regulates the assembly and DNA repair function of
an E3 ubiquitin ligase/ADP-ribosyltransferase complex. In Aim3 we will define the
contribution of the signaling axis to genome maintenance, tumorigenesis, and therapy
response. The enzymes that mediate DNA damage response and repair reactions have
emerged as actionable targets in malignancies including prostate cancer. Inhibitors to
the poly-ADP-ribosyltransferase family member, Parp1, improve outcomes in therapy-
resistant prostate cancer, though the benefit depends on the status of the DNA repair
machinery, notably the BRCA1/BRCA2 genotype. Thus, while the clinical findings
provide proof-of-principle for targeting DNA repair pathways, they also underscore the
importance of defining and incorporating biochemical and genomic context into
treatment rationale. In summary, our studies will define the biochemical relationships
between androgen signaling and DNA damage and repair pathways, and help provide
new insights into the vulnerabilities of prostate cancer cells.

## Key facts

- **NIH application ID:** 9873936
- **Project number:** 5R01CA214872-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Bryce Paschal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,908
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873936

## Citation

> US National Institutes of Health, RePORTER application 9873936, Parp Function in Prostate Cancer (5R01CA214872-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873936. Licensed CC0.

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