# Mechanistic Basis of Resistance to Chemohormonal Treatment in Prostate Cancer

> **NIH NIH F30** · NORTHWESTERN UNIVERSITY · 2020 · $50,520

## Abstract

PROJECT SUMMARY
In 2019, prostate cancer will be diagnosed in an estimated 174,650 men, and account for 31,620 deaths,
second only to lung cancer in terms of mortality for men. While local and regional disease typically carries an
excellent prognosis, prostate cancer is a heterogeneous and diverse disease that includes both indolent and
aggressive phenotypes. Androgen deprivation therapy (ADT) was the first successful treatment for men with
advanced metastatic prostate cancer more than 50 years ago, and it remains a cornerstone of treatment today,
but not all men will respond to ADT. The use of chemotherapy in combination with ADT significantly improved
upon ADT alone in terms of overall survival. Unfortunately, despite these advances, a significant portion of
men are resistance to combination chemohormonal therapy. The long-term goal of this proposal is to enable
more effective treatments for men with prostate cancer. This application proposes to address this goal by
investigating the mechanistic basis for chemohormonal resistance in prostate cancer using in vitro cellular
studies, in vivo murine models, and retrospective patient data.
Our laboratory has identified Paired-Related Homeobox Protein 2 (PRRX2) as contributing to ADT resistance
in vitro. Interestingly, PRRX2 is known to promote an epithelial to mesenchymal transition (EMT), which is
associated with chemoresistance in prostate cancer. However, the role of PRRX2-driven EMT has not been
investigated in the context of chemohormonal resistance. Therefore, my central hypothesis is that a PRRX2-
driven increase in EMT causes chemohormonal treatment resistance in prostate cancer. To test my
hypothesis, with Aim 1 I will determine the contribution of PRRX2 to EMT and chemohormonal resistance
using in vitro models of prostate cancer. In Aim 2, I will use in vivo mouse models determine the sufficiency of
PRRX2-driven EMT for chemohormonal resistance. Finally, in Aim 3, I will evaluate the clinical relevance of
my results by developing a gene signature of PRRX2-driven EMTness, and determining its association to
clinical features of prostate cancer using patient data. Together, these aims will fill a fundamental gap in the
understanding of prostate cancer pathogenesis, and allow for more effective treatments to be developed. I will
carry out these experiments under the mentorship of my sponsor, Dr. Sarki Abdulkadir, with his extensive
expertise in prostate cancer research. Dr. Abdulkadir will provide all of the necessary equipment and facilities,
and access to the core facilities of Northwestern University. The training plan set out by Dr. Abdulkadir will train
me as an independent researcher, while also maintaining my clinical skills to prepare me exceptionally well for
the next steps of my training as a physician scientist.

## Key facts

- **NIH application ID:** 9991545
- **Project number:** 1F30CA250248-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Zachary Rockow Chalmers
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991545

## Citation

> US National Institutes of Health, RePORTER application 9991545, Mechanistic Basis of Resistance to Chemohormonal Treatment in Prostate Cancer (1F30CA250248-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991545. Licensed CC0.

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