# Androgen Receptor Action in Castration Resistant Prostate Cancer

> **NIH NIH P01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $1,464,494

## Abstract

This is a revised competitive renewal application for our P01 entitled “Androgen Receptor Action In Castration
Resistant Prostate Cancer”. The past several years have seen a paradigm shift in prostate cancer (PCa)
therapy, as it is now clear that the androgen receptor (AR) remains active and is a therapeutic target in PCa
that relapses after surgical or medical castration (castration-resistant prostate cancer, CRPC). Previous basic,
translational and clinical research conducted by investigators in this P01 proposal made major contributions to
this paradigm shift by elucidating fundamental mechanisms of AR action and mechanisms of castration-
resistance in patients. The CYP17A1 inhibitor abiraterone, and the AR antagonist enzalutamide, are now
standard second line hormonal therapies for men who relapse after castration. Unfortunately, most men who
respond to these therapies will relapse within 1-2 years. Significantly, while a subset of abiraterone or
enzalutamide-resistant PCa may become AR independent, recent results from investigators in this P01 and
others indicate that most continue to express high levels of AR that appears to be transcriptionally active.
Therefore, a major hypothesis in this proposal is that AR activity still persists and is contributing to tumor
growth in abiraterone and enzalutamide-resistant PCa. Moreover, we hypothesize that adaptations made by
PCa cells in response to AR targeted therapies create vulnerabilities that can be exploited therapeutically.
Hence, overall program goals are to elucidate clinically relevant mechanisms that contribute to CRPC and
abiraterone/enzalutamide-resistance, to identify therapeutic approaches that can overcome these resistance
mechanisms and/or exploit new vulnerabilities, and to assess these therapeutic approaches in preclinical
models that can form foundations for clinical trials. The Projects are as follows: 1) Determining and Exploiting
Mechanisms of AR-Mediated Suppression of Cell, 2) Mechanisms Driving AR Full Length and Splice Variant
Activities and Antagonist Resistance, 3) Protein Kinases Influencing Androgen Receptor in Castrate Resistant
Prostate Cancer, 4) Identification of Essential Genes Underlying AR Activity in Antagonist-Resistant CRPC.

## Key facts

- **NIH application ID:** 9870878
- **Project number:** 5P01CA163227-07
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Steven P. Balk
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,464,494
- **Award type:** 5
- **Project period:** 2013-05-24 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870878

## Citation

> US National Institutes of Health, RePORTER application 9870878, Androgen Receptor Action in Castration Resistant Prostate Cancer (5P01CA163227-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9870878. Licensed CC0.

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