# Genomic analysis of prostate tumor heterogeneity in metastasis

> **NIH NIH R21** · EMORY UNIVERSITY · 2022 · $179,252

## Abstract

Summary: Prostate cancer is a highly heterogeneous disease, and mortality from prostate cancer is due to
metastases, and thus, understanding the mechanisms of metastasis is essential for improving patient
outcomes. In this proposal, we plan to leverage the resources of an ongoing NIH-funded clinical trial of patients
with high-risk prostate cancer who have had extensive dissection of surrounding lymph nodes and imaging
with the FDA-approved radiotracer [18F]-fluciclovine, a biomarker of amino acid transport, which is upregulated
in prostate cancer cells. We hypothesize that genomic analysis of multiple foci within the primary tumor, and
lymph nodes positive and negative for [18F]-fluciclovine uptake and metastatic disease, will provide new
insights into the mechanisms of the earliest steps in metastasis and help identify key driver mutations and
signal transduction pathways. We plan to test this hypothesis via the following specific aims: Aim 1) perform
whole exome sequencing of multiple primary foci and corresponding lymph nodes to identify somatic mutations
associated with LN mets; Aim 2) perform RNAseq analysis of multiple primary foci and corresponding lymph
nodes to identify gene expression changes associated with LN metastasis; Aim 3) determine RNA and DNA
signatures associated with the presence and degree of uptake of fluciclovine in LN mets. This proposal is
innovative in that we will be using multiple samples from the same patients to interrogate the heterogeneity of
primary prostate tumors and the genomic and gene expression changes that drive the initial step of metastasis
as they migrate to the lymph nodes. In addition, we will generate new understandings of the changes that are
associated with uptake of the radiotracer [18F]-fluciclovine, which reflects upregulated amino acid metabolism in
tumor cells. Discoveries from this project could lead to new approaches for treatment of advanced disease by
identifying the genomic changes essential to the first steps of metastasis and defining the biology of lethal
prostate cancer. New drug targets that are critical for metastasis may be identified from the knowledge gained
through this study.

## Key facts

- **NIH application ID:** 10314076
- **Project number:** 5R21CA256375-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Carlos Sanchez Moreno
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $179,252
- **Award type:** 5
- **Project period:** 2020-12-08 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314076

## Citation

> US National Institutes of Health, RePORTER application 10314076, Genomic analysis of prostate tumor heterogeneity in metastasis (5R21CA256375-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10314076. Licensed CC0.

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