# SPORE in Bladder Cancer

> **NIH NIH P50** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $896,275

## Abstract

Project Summary/Abstract
There is palpable excitement in the oncology community that we are on the cusp of a major advance in how we
treat bladder (urothelial) cancer. Recent efforts to comprehensively define the landscape of genetic alterations
in urothelial cancer and to understand their impact on drug sensitivity, as well as the exciting early results with
immune targeting strategies suggest that prospective molecular profiling of blood and tumor tissue could
improve the outcomes of urothelial cancer patients by personalizing care. This MSK SPORE in Bladder Cancer
seeks to leverage recently initiated multicenter efforts to explore the molecular basis of inherited genetic
susceptibility, exploit prospective molecular characterization to guide treatment, and to test the efficacy of
immunotherapy-based combination approaches. The overall translational aims of the MSK SPORE in Bladder
Cancer are to 1) develop predictive biomarkers of response and resistance to immunotherapy, chemotherapy,
and investigational treatments; 2) identify germline genetic alterations that confer increased risk for the
development of urothelial cancer; and 3) identify mechanisms of immunotherapy resistance and develop
combinatorial strategies to enhance immunotherapy response in patients with urothelial cancer. To pursue
these aims, we have assembled a multidisciplinary team with complementary expertise in the clinical
management of urothelial cancer, inheritable risk, mycobacterial and cancer biology, cancer genetics,
molecular pathology, biostatistics, computational biology, and multiplatform data integration. The translational
aims of this SPORE will be pursued through four projects, each of which addresses a different clinical state in
the evolution of the disease. Project 1 will use prospective molecular characterization to determine, in the
context of a cooperative group trial, whether transurethral resection and chemotherapy, without the need for
cystectomy, is curative in patients with DNA damage response gene alterations and to identify novel
biomarkers of chemotherapy sensitivity. Project 2 will identify and functionally characterize novel germline
variants that confer increased inherited susceptibility. Project 3 will seek to identify and validate tumor- and
blood-based predictive biomarkers of response to systemic immune checkpoint blockade in patients with
metastatic urothelial cancer in the context of a randomized, multicenter trial. Project 4 will seek to identify
predictive biomarkers of Bacillus Calmette-Guerin (BCG) response and BCG strains with greater activity as a
prelude to future clinical trials. Each of these projects will be supported by the Biospecimen Repository and the
Biostatistics and Bioinformatics Core, which will assist with the preparation and analysis of human tissues and
genomic, immune, and clinical data, and an Administrative Core will ensure project integration. Finally,
developmental research projects and career mentorship are fully...

## Key facts

- **NIH application ID:** 11196451
- **Project number:** 3P50CA221745-05S1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jonathan Eric Rosenberg
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $896,275
- **Award type:** 3
- **Project period:** 2018-08-24 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11196451

## Citation

> US National Institutes of Health, RePORTER application 11196451, SPORE in Bladder Cancer (3P50CA221745-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11196451. Licensed CC0.

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