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Similar Projects for

Project

Targeting the Regulation and Actions of Telomerase Reverse Transcriptase (TERT) in Bladder Cancer

Funder: Congressionally Directed Medical Research Programs

Funding period
USD 1.5 M
Funding amount
Abstract
PUBLIC ABSTRACT

Each year, over 81,000 Americans are diagnosed with bladder cancer. Bladder cancer is linked to environmental risk factors that are especially common in Veteran and active Service member populations, including exposure to tobacco, industrial solvents, radiation, and chemical weapons such as Agent Orange. Thus, unsurprisingly, bladder cancer is the fourth most frequently diagnosed cancer among Veterans.



Unfortunately, one third of bladder cancer patients suffer from advanced-stage tumors and have a high risk of dying from their cancer. Standard treatment often includes removal of the bladder in order to limit cancer spread. Even after surgery, cancer will return for half of these patients, and they will need to undergo aggressive chemotherapy and immunotherapy treatments. However, these treatments are only somewhat effective, and approximately 70% of patients with invasive bladder cancer die from the disease, leading to 17,240 deaths each year in the United States. Thus, there is an urgent need for new therapies to treat bladder cancer.



We aim to develop new therapies to treat bladder cancer by targeting genes and proteins that control tumor cell growth and survival. In human cells, the ends of DNA are capped by protective ends called telomeres. Telomerase, which includes the protein TElomerase Reverse Transcriptase (TERT), is an enzyme complex that extends the length of telomeres. Telomerase and TERT are critical for maintaining telomere length in stem cells as they rapidly grow and divide. However, telomerase activity is not needed in normal body cells, and telomerase genes are turned off. In tumor cells, telomerase often becomes active due to mutations in the part of the TERT gene that controls expression, called the promoter. These mutant TERT promoters are like having a gas pedal stuck in the “ON” position in your car. High telomerase activity protects the DNA inside tumor cells as they rapidly divide, leading to the notorious fast growth and immortality of cancer cells. Because these mutant TERT promoters are unique to cancer cells, targeting mutant TERT promoters may offer a new tactic we will use in our proposal for specifically attacking tumor cells while sparing normal, healthy cells. As of yet, no TERT therapies have been developed to treat cancer. We propose to find compounds that reduce the activity of the mutant TERT promoter (fix the damaged gas pedal so it turns off in cancer cells) and assess the ability of these compounds to limit tumor growth in mice.



Ultimately, this work will set the stage for the development of new drug therapies to treat patients with advanced-stage bladder cancer. New therapeutic options are critical for patients who do not respond to available immunotherapies and have no remaining treatment options. We expect that these patients will respond to mutant TERT promoter-directed therapy because about 70% of bladder cancers have TERT promoter mutations. Therapies that reduce mutant TERT promoter activity will lead to tumor cell death, which is known to stimulate the body’s immune response. By activating the immune system, TERT therapies may enhance the effect of existing immunotherapies, offering a powerful combination therapy. Mutant TERT promoters are also involved in the growth and survival of other incurable cancers, so our work has the potential to benefit an even greater number of patients. Based on our previous experience and current findings, we expect to bring a new TERT-based therapy to a Phase I clinical trial in the next 5 years. We are very excited to begin our work!

 
768
Projects
USD 374.6 M
Aggregated funding amount
USD 634 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
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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
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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
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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
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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
Project list item
Platform Selection for Biomarker Directed Radiotherapy for Bladder Cancer

NIHR Evaluation Trials and Studies Coordinating Centre to Catharine West

USD 51,871
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
A canine model for human high-risk non-muscle invasive human bladder cancer – molecular and environmental considerations.

V Foundation for Cancer Research to Matthew Breen

USD 500,000
2019 - 2021
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