Please enable JavaScript or talk to your local administrator to get JavaScript enabled.
Skip filters
Skip facets
Funder
  • 21

  • 15

  • 13

  • 11

  • 8

  • 4

  • 3

  • 3

  • 2

  • 2

Funder Group
Research Organization
FOR (ANZSRC) Category
RCDC Category
Researcher
City
State
Country
Country of Funder
Start Year
Active Year
Similar Projects for

Project

Investigating underlying molecular mechanisms of epigenetic therapies in muscle-invasive bladder cancer

Funder: Bladder Cancer Advocacy Network

Funding period
USD 2 K
Funding amount
Abstract
Lysine-specific demethylase 6A (KDM6A) and members of the Switch/Sucrose non-fermentable (SWI/SNF) family are known to counteract the activity of Enhancer of zeste homolog 2 (EZH2), which is often overexpressed and is associated with poor prognosis in muscle-invasive bladder cancer. Here we provide evidence that alterations in chromatin modifying enzymes, including KDM6A and members of the SWI/SNF complex, are frequent in muscle-invasive bladder cancer. We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2 based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. We reveal a novel mechanism of action of EZH2 inhibition, alone and in combination with cisplatin, which induces immune signaling with the largest changes observed in interferon gamma (IFN-?). This upregulation is a result of activated natural killer (NK) signaling as demonstrated by the increase in NK cell-associated genes MIP-1a, ICAM1, ICAM2, and CD86 in xenografts treated with EZH2 inhibitors. Conversely, EZH2 inhibition results in decreased expression of pluripotency markers, ALDH2 and CK5, and increased cell death. Our results reveal a novel sensitivity of muscle-invasive bladder cancer cells with KMD6A and SWI/SNF mutations to EZH2 inhibition alone and in combination with cisplatin. This sensitivity is mediated through increased NK cell-related signaling resulting in tumor cell differentiation and cell death.

 
91
Projects
USD 32.6 M
Aggregated funding amount
USD 447 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
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
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
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
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
Analysis of the antineoplastic action of Class I HDAC inhibitors to define new combination therapies for urothelial carcinoma

German Research Foundation to Günter Niegisch, Michèle Janine Hoffmann

 
2020 -
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 372,404
2019 - 2021
Project list item
Chromatin Modifier Gene Mutation and Enhancer Dysfunction in Bladder Cancer

National Cancer Institute to BYRON H LEE

USD 486,410
2019 - 2024
Project list item
Modeling bladder cancer pathogenesis and tumor evolution

National Cancer Institute to CORY ABATE-SHEN, MICHAEL M. SHEN, DAVID B SOLIT, HIKMAT AL-AHMADIE

USD 3,432,927
2018 - 2023
Project list item
Elucidating immunotherapy resistance mechanisms in non-T cell-inflamed bladder cancer

National Cancer Institute to RANDY F. SWEIS

USD 425,338
2018 - 2022
Project list item
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2020
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
Role of B-arrestins in bladder cancer progression and response to chemotherapy

United States Department of Veterans Affairs to BAL L LOKESHWAR

 
2018 - 2022
Project list item
Regulatory networks in basal-like bladder cancer

Fondation ARC pour la Recherche sur le Cancer to Jacqueline Fontugne

 
2017 - 2019
Project list item
Development of Classifiers for Novel Bladder Cancer Subtypes

Congressionally Directed Medical Research Programs to Woonyoung Choi

USD 856,134
2017 - 2018
Project list item
Development of Classifiers for Novel Bladder Cancer Subtypes

Congressionally Directed Medical Research Programs to Seungchan Kim

USD 706,947
2017 - 2018
Project list item
Targeting the Regulation and Actions of Telomerase Reverse Transcriptase (TERT) in Bladder Cancer

Congressionally Directed Medical Research Programs to Dan Theodorescu

USD 1,482,998
2017 - 2018
Project list item
Dissection of Suppressive Axes Underlying Natural Killer Cell Dysfunction in Human Bladder Cancer

Congressionally Directed Medical Research Programs to Nina Bhardwaj

USD 1,584,753
2017 - 2018
load more...