# Noninvasive, Uniplex, Molecular, Pathomic Urinary Assay for Detection of Prostate Cancer

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2022 · $582,001

## Abstract

Abstract: Despite the advances in understanding its genomic and molecular basis, prostate cancer (PCa)
remains the most commonly diagnosed solid malignancy in men in the US and the second leading cause of cancer
death. Currently, the only established method to diagnose PCa is an invasive transrectal ultrasound prostate
biopsy. The majority (>66%) of biopsies show benign pathology at the expense of patient morbidity and
healthcare dollars. There remains, therefore, an unmet need for a simple and non-invasive approach that will
definitively diagnose PCa, determine if it is aggressive, indolent or benign and help guide its management.
The era of molecular profiling has drawn much attention to genomic analysis of malignant PCa cells shed in blood
and urine. In two such assays, the PCA3 and SelectMDx approved by FDA, urine is collected after DRE, malignant
cells isolated and characterized by multiplex genomic finger prints of PCa. Although innovative, PCA3 test is not
widely used, primarily due to its wide range (62%-94%) of sensitivity, specificity, positive predictive (PPV) and
negative predictive value (NPV). Furthermore, the clinical utility of SelectMDx and a frequently advocated serum
4Kscore test, remains uncertain.
 There is robust literature demonstrating that VPAC receptors are expressed on PCa cells. With NIH/NCI
support, we designed and labeled a VPAC specific peptide with Cu-64 that allowed us to image PCa successfully in
humans. We then hypothesized that PCa cells, shed in voided urine of PCa patients, without prostate stimulation
by DRE, can be imaged optically by targeting VPAC receptors, using the same peptide labeled with a
fluorophore. Our preliminary results of >250 de-identified urine samples, collected from patients with PCa, BPH
and normal cases, are encouraging (sensitivity >98%) and are consistent with our hypothesis. In this investigation
we propose to obtain critical information that will be required for the development of this promising noninvasive
urine assay as a PCa diagnostic test. Our specific aims are 1) To determine sensitivity, specificity, positive
predictive (PPV), and negative predictive value (NPV) of the molecular urinary assay for men with known
PCa and negative controls; 2) To examine the efficacy of the assay in the management of patients with
previous negative biopsy for PCa but have persistently elevated PSA and are scheduled for TRUS biopsy;
3) To establish if a) the malignant cells as a percent of total cells shed in the urine, b) the fluorescence
intensity around malignant cells, and c) the VPAC protein quantity in shed malignant cells correlate with
the aggressiveness of the disease; 4) To assess the role of this molecular urine assay in the management
patients on active surveillance; and 5) To determine if a preservative is required for urine storage. This
simple, reliable and patient-friendly uniplex assay will a) detect active, aggressive or indolent PCa, b) save patients
from over diagnosis and ove...

## Key facts

- **NIH application ID:** 10427409
- **Project number:** 5R01CA249921-03
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Mathew Laxman Thakur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $582,001
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427409

## Citation

> US National Institutes of Health, RePORTER application 10427409, Noninvasive, Uniplex, Molecular, Pathomic Urinary Assay for Detection of Prostate Cancer (5R01CA249921-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427409. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*