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Combatting Bladder Cancer by Inducing Epithelial Turnover

Funder: National Cancer Institute

Funding period
USD 372 K
Funding amount
Abstract Bladder cancer is the 5th most frequent cancer in the US1. The most common histologic type of bladder cancer is urothelial carcinoma and it presents often as non-muscle invasive (NMIBC) form. The initial treatment for NMIBC is transurethral resection (TUR). However, over 70% of these patients will develop tumor recurrence with 25% showing progression to muscle-invading disease within 5 years of TUR. Currently, intravesicular BCG-based immunotherapy and chemotherapy are widely used as adjuvant therapies after TUR, but their effectiveness is limited, due to side effects and/or the inability of therapeutic agents to penetrate the bladder mucosa. Thus there exists a dire need for new strategies as adjunct therapy for bladder cancer. Recently, the whole scale exfoliation of the superficial epithelium mediated by the bladder to reduce bacterial numbers during infection was found to be a specific mast cell (MC) mediated activity. Further it was possible to activate whole scale exfoliation of the bladder epithelium by merely administering a MC activator in the bladder lumen. Although a highly efficient re-epithelization program exists for bladder epithelium recovery, addition of a GAG layer to the exposed bladder wall soon after exfoliation was found to significantly enhance the speed and intensity of bladder recovery. In view of this ability to trigger rapid turnover of the bladder epithelium, we hypothesize that safely inducing bladder epithelial turnover is a powerful way to prevent recurrence of bladder cancer. Here we plan to Investigate if inducing epithelial turnover with MC activators in the bladder will reduce/eliminate tumors in the bladders of mice. We will also Investigate if administering a GAG matrix containing growth promoting and/or anti-inflammatory agents will accelerate reepithelization following induced epithelial loss.

USD 213.8 M
Aggregated funding amount
USD 592 K
Average funding amount
Project list item
Intravesical delivery of an Fc-enhanced CD40 agonist antibody for the treatment of bladder cancer

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Epigenetic regulators of subtype plasticity in bladder cancer

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Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer


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Implication of neutrophil extracellular traps in the efficacy of bladder-sparing therapy in muscle invasive bladder cancer

Canadian Institutes of Health Research to Wassim Kassouf, Ciriaco A. Piccirillo, Jonathan David Spicer

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CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
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A new bladder cancer model based on tissue reprogramming and gene targeting

National Cancer Institute to FLAMINIA TALOS, DAIFENG WANG

USD 203,843
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Roles of epigenetic regulators in bladder cancer progression

University of California - Cancer Research Coordinating Committee to Zhu Wang

USD 74,960
2020 - 2020
Project list item
Chemotherapy plus PD-1 blockade as bladder-sparing treatment for muscle-invasive bladder cancer

V Foundation for Cancer Research to Matthew D Galsky

USD 600,000
2019 - 2022
Project list item
Unravelling Mechanisms of Resistance to Checkpoint Inhibition in Canine Urothelial Carcinoma

V Foundation for Cancer Research to Nicola J. Mason

USD 500,000
2019 - 2021
Project list item
Engineering Smart Solutions for Disorders of the Bladder Urothelium

Engineering and Physical Sciences Research Council

2019 - 2023
Project list item
Implementing Risk-aligned Bladder Cancer Surveillance

United States Department of Veterans Affairs to FLORIAN R SCHROECK

2019 - 2023
Project list item
[The association between SORL1 and advanced bladder cancer] - Original in Japanese

Japan Society for the Promotion of Science to Takanobu UTSUMI

USD 26,335
2019 - 2021
Project list item
Geriatric Conditions and Treatment Burden in Older Adults with Non-Muscle-Invasive Bladder Cancer and Their Caregivers

National Institute on Aging to TULLIKA GARG

USD 271,698
2019 - 2021
Project list item
Developing a SMART scaffold for bladder augmentation

National Institute of Biomedical Imaging and Bioengineering to GUILLERMO ANTONIO AMEER, JOHN ROGERS, ARUN SHARMA

USD 1,399,891
2019 - 2023
Project list item
Investigating underlying molecular mechanisms of epigenetic therapies in muscle-invasive bladder cancer

Bladder Cancer Advocacy Network to Swathi Ramakrishnan

USD 1,700
2019 - 2019
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