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Characterization of mutational signatures, gene expression patterns and immune populations in metastatic nodal and bladder tumor tissue to predict response to primary chemotherapy in node positive bladder cancer.

Funder: Bladder Cancer Advocacy Network

Funding period
USD 2 K
Funding amount
Abstract
Research ProposalBackgroundPatients with metastatic bladder cancer limited to the pelvic lymph nodes have improved rates of response to chemotherapy and better outcomes compared to those with widely metastatic disease. Research identifying biomarkers or subtypes to predict sensitivity to chemotherapy exclude node positive patients or only make up only a small subset. Additionally, these studies use bladder tumor tissue for analysis and have not analyzed lymph node positive tissue. This assumes that bladder tumors are surrogate predictors for response of micrometastatic or metastatic disease to the nodes, which is unknown. This is an important distinction as there may be unique signatures within the lymph node positive tissue not present in bladder tumor that can better predict response to chemotherapy. Interestingly, molecular subtype classification of bladder tumor tissue can be distinct from synchronous lymph node tissue. HypothesisDistinct mutational signatures, gene expression patterns and immune landscapes in node positive tissue more accurately predicts nodal response to chemotherapy and outcomes compared to matched bladder tumors. MethodsData was retrospectively collected from patients with cTanyN1-3M0 bladder cancer who underwent radical cystectomy at the University of Texas MD Anderson Cancer Center. A subset of these patients underwent lymph node biopsy prior to chemotherapy to determine true nodal status. Nodal and bladder response to chemotherapy was based on final pathology at cystectomy. Recurrence free and overall survival were determined. Next Generation Sequencing and mass spectrometry based methods (cytometry by time of flight, i.e. CyTOF) will be used to identify unique markers in bladder tumor and matched node tissue from biopsy prior to chemotherapy to identify novel immune signatures and molecular markers of predictors of response to chemotherapy.

 
319
Projects
USD 153.6 M
Aggregated funding amount
USD 541 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
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, Kiu Yan Charlotte Ng, Marianna Kruithof-de Julio, Franziska Singer

USD 702,564
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
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
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
The role of a new molecular driver in bladder cancer

National Cancer Institute to DALEY MORERA

USD 45,016
2018 - 2021
Project list item
A co-clinical trial of chemotherapy response in bladder cancer using patient-derived tumor organoids

V Foundation for Cancer Research to Michael M Shen

USD 600,000
2018 - 2021
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
Project list item
Elucidating immunotherapy resistance mechanisms in non-T cell-inflamed bladder cancer

National Cancer Institute to RANDY F. SWEIS

USD 212,669
2018 - 2022
Project list item
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2019
Project list item
SPORE in Bladder Cancer

National Cancer Institute to DEAN F. BAJORIN, TIMOTHY AN-THY CHAN, IRINA OSTROVNAYA, HIKMAT AL-AHMADIE, MICHAEL STEPHEN GLICKMAN, DAVID B SOLIT

USD 2,299,837
2018 - 2023
Project list item
Modeling bladder cancer metastasis using human patient-derived tumor organoids

Bladder Cancer Advocacy Network to Michael M Shen

USD 300,000
2018 - 2020
Project list item
Upper tract urothelial carcinoma is non-basal and T-cell depleted

Bladder Cancer Advocacy Network to Panagiotis Vlachostergios

USD 1,700
2018 - 2018
Project list item
Novel Biomarkers for the Clinical Management of Bladder Cancer

National Cancer Institute to VINATA B LOKESHWAR

USD 466,211
2018 - 2023
Project list item
Circulating tumor DNA as a predictive biomarker in metastatic bladder cancer

Canadian Institutes of Health Research to Gillian Rae Vandekerkhove, Alexander William Wyatt

USD 53,221
2018 - 2021
Project list item
Intra-operative MRI-guided Robotic System for Photothermal Therapy of Bladder Cancer

University Grants Committee to Kwok Ka Wai, Wong Kenneth Kin Yip, Vardhanabhuti Varut Vince, TEOH Yuen Chun Jeremy

USD 80,682
2018 - 2021
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