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Similar Projects for

Project

The role of a new molecular driver in bladder cancer

Funder: National Cancer Institute

Funding period
USD 90 K
Funding amount
Abstract
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.

 
1,069
Projects
USD 505.4 M
Aggregated funding amount
USD 619 K
Average funding amount
Project list item
Intravesical delivery of an Fc-enhanced CD40 agonist antibody for the treatment of bladder cancer

Bladder Cancer Advocacy Network to Jeffrey Ravetch, David Knorr

USD 300,000
2020 - 2022
Project list item
Epigenetic regulators of subtype plasticity in bladder cancer

Bladder Cancer Advocacy Network to John Robert Christin

USD 1,700
2020 - 2020
Project list item
Characterization of Nectin-4 expression in molecular subtypes of urothelial cancer and mechanisms of resistance to enfortumab vedotin

Bladder Cancer Advocacy Network to Carissa Ellen Chu

USD 1,700
2020 - 2020
Project list item
Recombinant CCL2 as a novel treatment strategy for bladder cancer

Bladder Cancer Advocacy Network to Neelam Mukherjee, Robert Scott Svatek

USD 50,000
2020 - 2021
Project list item
Defining NRF2 induced tumor invasion in bladder cancer

Bladder Cancer Advocacy Network to Yuki Kita, William Youngkwan Kim, Bernard Weissman

USD 50,000
2020 - 2021
Project list item
Targeting regulatory B cells (Bregs) to improve anti-bladder cancer immunity

Bladder Cancer Advocacy Network to Burles Avner Johnson, David McConkey

USD 50,000
2020 - 2021
Project list item
Alpha1H: A Unique Bladder Cancer Therapeutic, Acting with Great Precision

European Commission

USD 2,452,885
2020 - 2022
Project list item
Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer

National Cancer Institute to NINA BHARDWAJ, JUN ZHU, MATTHEW GALSKY

USD 703,400
2020 - 2025
Project list item
SGLT-2 Inhibitors and Early Bladder Cancer Events: An International Multi-Centre Study

Canadian Institutes of Health Research to Elisabetta Patorno, Laurent Azoulay, Devin Abrahami, Lysanne Campeau, Blanaid Hicks, Robert William Platt, Sebastian Schneeweiss, Oriana Hoi Yun Yu

USD 88,269
2020 - 2022
Project list item
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

USD 138,878
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
Analysis of the effect of IDO inhibition on activation of the aryl hydrocarbon receptor pathway in bladder cancer

São Paulo Research Foundation to Humberto Dellê

 
2020 - 2021
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
Identification and analysis of early prognostic markers of bladder cancer using generated nanobodies

Russian Science Foundation to Sergei Tillib

 
2020 - 2022
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
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