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The role of a new molecular driver in bladder cancer

Funder: National Cancer Institute

Funding period
USD 90 K
Funding amount
PROJECT SUMMARY Bladder cancer is a common cancer of the urinary tract with 79,000 new cases diagnosed in the US each year. A bladder tumor may be low-grade or high-grade. While low-grade tumors are most often confined to the urothelial layer, high-grade tumors often invade into the muscle layer of the bladder. A tumor that is confined to the urothelial layer is resected from the bladder; however, muscle invasive tumors require surgical removal of the bladder and adjuvant chemotherapy if there is metastasis. This high metastatic potential of high-grade tumors is responsible for the significant morbidity and mortality associated with bladder cancer. Two-thirds of patients with high-grade tumors have muscle-invasive disease at initial presentation. Fifty percent of patients with muscle- invasive bladder cancer will develop metastasis within two years, and the five-year survival of patients with metastatic disease is only 15%, despite chemotherapy. Identification of tumor promoting molecular pathways in bladder cancer could lead to the development of molecular markers that can identify patients who are likely to develop metastasis, and individualize selection of chemotherapy regimens. This could significantly improve the clinical management of patients with muscle-invasive disease. Proteoglycans have been shown to regulate tumor growth, progression, and chemoresistance. However, the role of proteoglycan-degrading enzymes (PDEs) is not well understood in benign or malignant diseases. Identification and characterization of a novel PDE showed that expression of this enzyme promotes malignant phenotype and chemotherapeutic resistance in bladder cancer and normal urothelial cells. The expression of this PDE was elevated in bladder tumor tissues and correlated with malignant progression of the disease and response to adjuvant chemotherapy. This project is designed to test a hypothesis that the activity of the PDE and its downstream effectors drive a malignant phenotype (muscle invasion, metastasis) and chemoresistance in bladder cancer and associate with poor clinical outcome. The hypothesis will be tested by mapping the functional domains in the PDE that are responsible for its enzymatic and biological activities and identifying downstream effectors that drive the PDE-induced malignant behavior (Aim 1). The expression and the activity of the PDE together with molecular effectors identified in Aim 1 will be validated in bladder cancer specimens and correlated with clinical outcome (Aim 2). Impact: This project will be the first study to evaluate a novel PDE that is potentially a molecular determinant of advanced bladder cancer and chemoresistance. Understanding the mechanism by which PDE induces malignant phenotype and chemoresistance, and the association of the PDE and its effectors with clinical outcome, if successful, may improve clinical management patients through the development of new molecular markers and therapeutic targets for aggressive bladder cancer.

USD 483.5 M
Aggregated funding amount
USD 618 K
Average funding amount
Project list item
Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer


USD 703,400
2020 - 2025
Project list item
Chimeric RNAs and their implication in lymphatic metastasis of bladder cancer

National Cancer Institute to HUI LI

USD 205,913
2020 - 2025
Project list item
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
Project list item
Effect of APOBEC3 on Bladder Cancer Biology and Response to Immunotherapy

National Cancer Institute to ANDREW TRUONG

USD 45,016
2020 - 2023
Project list item
A new bladder cancer model based on tissue reprogramming and gene targeting

National Cancer Institute to FLAMINIA TALOS, DAIFENG WANG

USD 203,843
2020 - 2021
Project list item
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
Quantifying Risk and Resilience (R2) among Patients with Bladder Cancer: A Novel Personalized, Comprehensive Risk Stratification Program

Bladder Cancer Advocacy Network to Sarah Psutka, Jonathan Wright, Daniel Lin, John Gore, Ryan O'Malley, Anne Browning, Florian Fintelmann

USD 50,000
2020 - 2021
Project list item
Engineering Smart Solutions for Disorders of the Bladder Urothelium

Engineering and Physical Sciences Research Council

2019 - 2023
Project list item
Bladder cancer chemotherapy potentiation with a multiprong arachidonic acid pathway modulator

National Cancer Institute to PAUL THOMAS HENDERSON

USD 300,000
2019 - 2020
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 135,849
2019 - 2021
Project list item
Developing a SMART scaffold for bladder augmentation

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

USD 709,004
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
Project list item
Transdifferentiation of fibroblasts to urothelial progenitors for definitive urothelial replacement therapy in non-muscle invasive bladder cancer

Bladder Cancer Advocacy Network to Philip A Beachy, Kris Butalid Prado

USD 300,000
2019 - 2021
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