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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 45 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.

 
933
Projects
USD 457.9 M
Aggregated funding amount
USD 547 K
Average funding amount
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
Recombinant CCL2 as a novel treatment strategy for bladder cancer

Bladder Cancer Advocacy Network to Neelam Mukherjee, Robert Scott Svatek

USD 50,000
2019 - 2020
Project list item
Understanding the Burden and Impact of Financial Toxicity in Bladder Cancer: A Mixed Methods Study of 2 Diverse Patient Populations

Bladder Cancer Advocacy Network to Sumeet Kaur Bhanvadia, Siamak Daneshmand, Reginald Tucker-Seeley

USD 50,000
2019 - 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
2019 - 2020
Project list item
Targeting FGF in Bladder cancer after Neoadjuvant Immunotherapy and Surgery

American Association For Cancer Research to Joshua James Meeks

USD 25,000
2019 - 2020
Project list item
Biomarker-Based Tools for Treatment Response Decision Support of Bladder Cancer

National Cancer Institute to LUBOMIR M HADJIYSKI, AJJAI SHIVARAM ALVA

USD 653,319
2019 - 2024
Project list item
Refined phenotyping and personalized targeting of muscle-invasive bladder cancer

Swiss National Science Foundation to Roland Seiler, Vera Genitsch, Franziska Singer, Kiu Yan Charlotte Ng, Marianna Kruithof-de Julio

USD 597,404
2019 - 2023
Project list item
DNA adductome of human bladder from the tobacco exposome

National Institute of Environmental Health Sciences to ROBERT J. TURESKY

USD 467,974
2019 - 2023
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 203,510
2019 - 2021
Project list item
Chromatin Modifier Gene Mutation and Enhancer Dysfunction in Bladder Cancer

National Cancer Institute to BYRON H LEE

USD 243,205
2019 - 2024
Project list item
Raman Endoscopic Proteo-lipidomics of Bladder Cancer

European Research Council to Mads SYLVEST BERGHOLT

USD 1,705,861
2019 - 2024
Project list item
Phase 1/2 Study of Modern Immunotherapy in BCG-Relapsing Urothelial Carcinoma of the Bladder - (ADAPT-BLADDER)

National Cancer Institute to NOAH M HAHN

USD 656,816
2019 - 2024
Project list item
Development of an automated method to capture bladder cancer recurrence and progression for epidemiologic research

National Cancer Institute to KIM N DANFORTH

USD 172,270
2019 - 2021
Project list item
Defining the impact of intra-tumoral morphologic, immune and mutational heterogeneity in urothelial carcinoma

National Cancer Institute to HIKMAT AL-AHMADIE

USD 410,835
2019 - 2024
Project list item
Multi4 - a new surgical instrument for diagnosis and treatment of bladder cancer within cystoscopy

VINNOVA to Miden Melle-Hannah

USD 55,963
2019 - 2019
Project list item
Identifying DNA Biomarkers of Bacillus Calmette-Guerin (BCG) Resistance in Non-Muscle-Invasive Bladder Cancer

Canadian Institutes of Health Research to Jack Victor Warren Bacon, Alexander William Wyatt

USD 847
2018 - 2019
Project list item
Modulation of regulatory T cells in the bladder tumor environment by anti-PD-L1 immunotherapy

Bladder Cancer Advocacy Network to David Yoonsuk Oh, Lawrence Fong

USD 50,000
2018 - 2019
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