# Analysis of urine tumor nucleic acids for detection and personalized surveillance of bladder cancer

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $559,757

## Abstract

PROJECT SUMMARY
Bladder cancer (BC) is the sixth most common cancer in the U.S., has one of the highest recurrence rates of
all solid cancers, and is the most expensive cancer to treat from diagnosis to death. There are significant
unmet needs for biomarkers and molecular diagnostic tools to better inform decision making across all stages
of BC. This includes prediction of treatment response in patients with non-muscle invasive (NMIBC) and
muscle invasive bladder cancer (MIBC), as well as improving diagnostic yield in patients undergoing screening
cystoscopy for hematuria. Our long-term goal is to improve outcomes for BC patients through the
development and application of molecular biomarkers that facilitate personalized approaches to
detection and treatment.
Urine is an attractive source for development of BC diagnostics and we recently developed a novel strategy for
detecting urine tumor DNA called urine tumor DNA Cancer Personalized Profiling by Deep Sequencing
(uCAPP-Seq). Our preliminary data indicate that uCAPP-Seq has outstanding sensitivity and specificity for
detection and surveillance of BC. In this project we will prospectively collect urine and other biospecimens from
patients with or at risk for BC and will test the potential clinical utility of uCAPP-Seq in different clinical
scenarios. We will also test if augmenting uCAPP-Seq with analysis of urinary RNA or DNA methylation further
augments performance. Our central hypothesis is that uCAPP-Seq will enable monitoring of BC
responses during and after treatment for NMIBC and MIBC. Furthermore, we hypothesize that
combining analysis of urine DNA mutations, DNA methylation, and urine RNA will allow ultrasensitive
and specific early detection of BC. We propose three specific aims: 1) To assess the value of urine tumor
DNA for non-invasive response assessment and monitoring in patients with high risk NMIBC treated with
bacillus Calmette-Guérin (BCG) immunotherapy; 2) To determine if urine tumor DNA analysis can predict
pathologic complete responses to neoadjuvant chemotherapy in patients with MIBC; and 3) To develop a
Bladder Cancer Interception Assay (BCIA) which integrates utDNA mutations and methylation with urinary
RNA for ultra-sensitive detection of bladder cancer.
Successful completion of the studies proposed here will serve as a foundation for incorporating our novel
urine-based biomarkers into prospective clinical trials. We foresee that our approach will allow personalization
of treatment strategies to improve outcomes for BC patients. Importnatly, our work will serve as proof-of-
principle for an approach that could also be applied to other genitourinary cancer types.

## Key facts

- **NIH application ID:** 10880419
- **Project number:** 5R01CA244526-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ash Arash Alizadeh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $559,757
- **Award type:** 5
- **Project period:** 2020-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880419

## Citation

> US National Institutes of Health, RePORTER application 10880419, Analysis of urine tumor nucleic acids for detection and personalized surveillance of bladder cancer (5R01CA244526-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10880419. Licensed CC0.

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